EGSnrc is a general-purpose software toolkit that can be applied to build Monte Carlo simulations of coupled electron-photon transport, for particle energies ranging from 1 keV to 10 GeV. It is widely used internationally in a variety of radiation-related fields. The EGSnrc implementation improves the accuracy and precision of the charged particle transport mechanics and the atomic scattering cross-section data. [ 4 ] [ 5 ] [ 6 ]  The charged particle multiple scattering algorithm allows for large step sizes without sacrificing accuracy - a key feature of the toolkit that leads to fast simulation speeds. [ 7 ] [ 8 ]  EGSnrc also includes a C++ class library called egs++ that can be used to model elaborate geometries and particle sources.


EGSnrc is open source and distributed on  GitHub  under the  GNU Affero General Public License . Download EGSnrc for free, submit bug reports, and contribute pull requests on a group GitHub page. [ 9 ]  The documentation for EGSnrc is also available online. [ 10 ]


EGSnrc is distributed with a wide range of applications that utilize the radiation transport physics to calculate specific quantities. These codes have been developed by numerous authors over the lifetime of EGSnrc to support the large user community. It is possible to calculate quantities such as  absorbed dose ,  kerma , particle fluence, and much more, with complex geometrical conditions. One of the most well-known EGSnrc applications is BEAMnrc, which was developed as part of the OMEGA project. This was a collaboration between the  National Research Council of Canada  and a research group at the  University of Wisconsin–Madison . All types of medical  linear accelerators  can be modelled using the BEAMnrc's component module system. [ 11 ]


This  scientific software  article is a  stub . You can help Wikipedia by  expanding it .


Electron therapy  or  electron beam therapy  ( EBT ) is a kind of  external beam radiotherapy  where  electrons  are directed to a  tumor  site for medical treatment of cancer.


Electron beam therapy is performed using a medical  linear accelerator . The same device can also be used to produce high energy photon beams. When electrons are required, the X-ray target is retracted out of the beam and the electron beam is  collimated  with a piece of apparatus known as an applicator or an additional collimating insert, constructed from a low melting point alloy.


Electron beams have a finite range, after which dose falls off rapidly. Therefore, they spare deeper healthy tissue. The depth of the treatment is selected by the appropriate energy.  Unlike photon beams there is no surface sparing effect, so electron therapy is used when the target extends to the patient's  skin .


Electron beam therapy is used in the treatment of superficial tumors like cancer of skin regions, or total skin (e.g.  mycosis fungoides ), diseases of the limbs (e.g.  melanoma  and  lymphoma ), nodal irradiation, and it may also be used to boost the radiation dose to the surgical bed after  mastectomy  or  lumpectomy . For deeper regions  intraoperative electron radiation therapy  might be applied.


ESTRO  (The European Society for Radiotherapy and Oncology) [ 1 ]  is a  scientific society  established in 1980 in  Milan ,  Italy , [ 2 ] [ 3 ] [ 4 ]  founded by  Maurice Tubiana ,  Jerzy Einhorn , [ 5 ]   Klaas Breur , [ 6 ]   Michael Peckham , [ 7 ]  and  Emmanuel van der Schueren . It aims to advance  radiation oncology  to improve  cancer treatment  outcomes through education, research, and quality assurance. ESTRO is based in  Brussels ,  Belgium . It is governed by an elected Board and has several committees focused on areas such as education, science, and clinical practice. The society collaborates with other oncology organizations and works to promote radiation oncology at the European level. [ 8 ]


ESTRO supports its members through various initiatives:


A  gallium scan  is a type of  nuclear medicine  test that uses either a  gallium-67  ( 67 Ga) or  gallium-68  ( 68 Ga)  radiopharmaceutical  to obtain images of a specific type of tissue, or disease state of tissue.  Gallium   salts  like gallium  citrate  and gallium  nitrate  may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga 3+  which is active. [ 1 ]  Both  67 Ga and  68 Ga salts have similar uptake mechanisms. [ 2 ]  Gallium can also be used in other forms, for example  68 Ga-PSMA is used for  cancer  imaging. The  gamma emission  of gallium-67 is imaged by a  gamma camera , while the  positron emission  of gallium-68 is imaged by  positron emission tomography  (PET).


Gallium salts are taken up by tumors, inflammation, and both acute and chronic infection, [ 3 ] [ 4 ]  allowing these pathological processes to be imaged. Gallium is particularly useful in imaging  osteomyelitis  that involves the spine, and in imaging older and chronic infections that may be the cause of a  fever of unknown origin . [ 5 ] [ 6 ]


Gallium-68 DOTA scans are increasingly replacing octreotide scans (a type of  indium-111  scan using octreotide as a somatostatin receptor ligand). The gallium-68 is bound to an octreotide derivative chemical such as  DOTATOC  and the positrons it emits are imaged by  PET-CT  scan. Such scans are useful in locating  neuroendocrine tumors  and  pancreatic cancer . [ 7 ] [ 8 ]


In the past, the gallium scan was the  gold standard  for  lymphoma  staging, until it was replaced by  positron emission tomography  (PET) using  fludeoxyglucose  (FDG). [ 9 ] [ 10 ]  Gallium imaging is still used to image inflammation and  chronic  infections, and it still sometimes locates unsuspected tumors as it is taken up by many kinds of cancer cells in amounts that exceed those of normal tissues. Thus, an increased uptake of gallium-67 may indicate a new or old infection, an inflammatory focus from any cause, or a cancerous tumor.


It has been suggested that gallium imaging may become an obsolete technique, with  indium leukocyte imaging  and  technetium antigranulocyte  antibodies replacing it as a detection mechanism for infections. For detection of  tumors , especially lymphomas, gallium imaging is still in use, but may be replaced by  fludeoxyglucose  PET imaging in the future. [ 11 ]


In infections, the gallium scan has an advantage over indium leukocyte imaging in imaging  osteomyelitis  (bone infection) of the spine, lung infections and inflammation, and for chronic infections. In part this is because gallium binds to  neutrophil  membranes, even after neutrophil death. Indium leukocyte imaging is better for acute infections (where neutrophils are still rapidly and actively localizing to the infection), and also for osteomyelitis that does not involve the spine, and for  abdominal  and  pelvic  infections. Both the gallium scan and indium leukocyte imaging may be used to image  fever of unknown origin  (elevated temperature without an explanation). However, the indium leukocyte scan will image only the 25% of such cases which are caused by acute infections, while gallium will also localize to other sources of fever, such as chronic infections and tumors. [ 12 ] [ 13 ]


The body generally handles Ga 3+  as though it were  ferric  iron (Fe-III), and thus the free isotope ion is bound (and concentrates) in areas of inflammation, such as an infection site, and also areas of rapid cell division. [ 14 ]  Gallium (III) (Ga 3+ ) binds to  transferrin ,  leukocyte   lactoferrin ,  bacterial   siderophores ,  inflammatory proteins , and cell-membranes in neutrophils, both living and dead. [ 15 ]


Lactoferrin is contained within leukocytes. Gallium may bind to lactoferrin and be transported to sites of inflammation, or binds to lactoferrin released during bacterial  phagocytosis  at infection sites (and remains due to binding with  macrophage  receptors). [ 16 ]  Gallium-67 also attaches to the siderophore molecules of bacteria themselves, and for this reason can be used in  leukopenic  patients with bacterial infection (here it attaches directly to bacterial proteins, and leukocytes are not needed). [ 17 ]  Uptake is thought to be associated with a range of tumour properties including transferring receptors, anaerobic tumor metabolism and tumor perfusion and  vascular permeability . [ 18 ] [ 19 ]


Note that all of these conditions are also seen in PET scans using the gallium-68.


The main ( 67 Ga) technique uses  scintigraphy  to produce two-dimensional images. After the tracer has been injected, images are typically taken by a  gamma camera  at 24, 48, and in some cases, 72, and 96 hours later. [ 23 ] [ 24 ]  Each set of images takes 30–60 minutes, depending on the size of the area being imaged. The resulting image will have bright areas that collected large amounts of tracer, because inflammation is present or rapid cell division is occurring.  Single-photon emission computed tomography  (SPECT) images may also be acquired. In some imaging centers, SPECT images may be combined with  computed tomography  (CT) scan using either fusion software or SPECT/CT hybrid cameras to superimpose both physiological image-information from the gallium scan, and anatomical information from the CT scan.


A common injection dose is around 150  megabecquerels . [ 25 ]  Imaging should not usually be sooner than 24 hours as high background at this time produces false negatives. Forty-eight-hour whole body images are appropriate. Delayed imaging can be obtained even 1 week or longer after injection if bowel is confounding. SPECT can be performed as needed. Oral laxatives or enemas can be given before imaging to reduce bowel activity and reduce dose to large bowel; however, the usefulness of bowel preparation is controversial. [ 24 ]


10% to 25% of the dose of gallium-67 is excreted within 24 hours after injection (the majority of which is excreted through the kidneys). After 24 hours the principal excretory pathway is colon. [ 24 ]  The "target organ" (organ that receives the largest radiation dose in the average scan) is the colon (large bowel). [ 23 ]


In a normal scan, uptake of gallium is seen in wide range of locations which do not indicate a positive finding. These typically include soft tissues,  liver , and bone. Other sites of localisation can be  nasopharyngeal  and  lacrimal  glands, breasts (particularly in  lactation  or  pregnancy ), normally healing wounds, kidneys, bladder and colon. [ 26 ]


The positron emitting isotope,  68 Ga, can be used to target  prostate-specific membrane antigen  (PSMA), a  protein  which is present in  prostate cancer  cells. The technique has been shown to improve detection of  metastatic  disease compared to  MRI  or  CT scans . [ 27 ]


In December 2020, the U.S.  Food and Drug Administration  (FDA) approved  68 Ga PSMA-11  for medical use in the United States. [ 28 ] [ 29 ]  It is  indicated  for positron emission tomography (PET) of prostate specific membrane antigen (PSMA) positive lesions in men with prostate cancer. [ 30 ] [ 29 ]  It is manufactured by the UCLA Biomedical Cyclotron Facility. [ 29 ]  The FDA approved  68 Ga PSMA-11 based on evidence from two clinical trials (Trial 1/NCT0336847 identical to NCT02919111 and Trial 2/NCT02940262 identical to NCT02918357) of male participants with prostate cancer. [ 29 ]  Some participants were recently diagnosed with the prostate cancer. [ 29 ]  Other participants were treated before, but there was suspicion that the cancer was spreading because of rising prostate specific antigen or PSA. [ 29 ]  The trials were conducted at two sites in the United States. [ 29 ]


The FDA considers  68 Ga PSMA-11 to be a  first-in-class medication . [ 31 ]


Gallium PSMA scanning is recommended primarily in cases of  biochemical recurrence  of prostate cancer, particularly for patients with low  PSA  values, and in patients with high risk disease where metastases are considered likely. [ 32 ] [ 33 ]


An  intravenous  administration of 1.8–2.2  megabecquerels  of  68 Ga PSMA-11 per  kilogram  of bodyweight is recommended. Imaging should commence approximately 60 minutes after administration with an acquisition from mid-thigh to the base of the skull. [ 32 ] [ 34 ]


68 Ga  DOTA  conjugated  peptides  (including  68 Ga  DOTA-TATE ,  DOTA-TOC  and  DOTA-NOC ) are used in  positron emission tomography  (PET) imaging of  neuroendocrine tumours  (NETs). The scan is similar to the SPECT  octreotide scan  in that an octreotide-based  somatostatin  analogue (such as  edotreotide ) is used as the  radioligand , and there are similar  indications  and uses as ocreotide scans, however image quality is significantly improved. [ 35 ]  Somatostatin receptors are overexpressed in many NETs, so that the  68 Ga DOTA conjugated peptide is preferentially taken up in these locations, and visualised on the scan. [ 36 ]  As well as diagnosis and staging of NETs,  68 Ga DOTA conjugated peptide imaging may be used for planning and  dosimetry  in preparation for  lutetium -177 or  yttrium-90  DOTA  therapy . [ 37 ] [ 38 ]


In June 2016, Netspot (kit for the preparation of gallium Ga-68 dotatate injection) was approved for medical use in the United States. [ 39 ] [ 40 ]


In August 2019,  68 Ga  edotreotide  injection ( 68 Ga DOTATOC) was approved for medical use in the United States for use with PET imaging for the localization of somatostatin receptor positive neuroendocrine tumors (NETs) in adults and children. [ 41 ] [ 42 ] [ 43 ]


The U.S.  Food and Drug Administration  (FDA) approved  68 Ga  edotreotide  (DOTATOC) based on evidence from three clinical trials (Trial 1/NCT#1619865, Trial 2/NCT#1869725, Trial 3/NCT#2441062) of 334 known or suspected neuro-endocrine tumors. [ 42 ]  The trials were conducted in the United States. [ 42 ]


Gallium ( 68 Ga) oxodotreotide was approved for medical use in Canada as Netspot in July 2019, [ 44 ]  and as Netvision in May 2022. [ 45 ]


The combination germanium (68Ge) chloride / gallium (68Ga) chloride was approved for medical use in the European Union in August 2024. [ 46 ]


Other gallium-68 based PET scanning agents may also be based on the principle of attaching peptides to chelators, such as the in-development drug  Ga-68-Trivehexin .


Gallium-67 citrate is produced by a cyclotron. Charged particle bombardment of enriched Zn-68 is used to produce gallium-67. The gallium-67 is then complexed with citric acid to form gallium citrate. The half-life of gallium-67 is 78 hours. [ 47 ]  It decays by  electron capture , then emits de-excitation  gamma rays  that are detected by a gamma camera. Primary emission is at 93  keV  (39% abundance), followed by 185 keV (21%) and 300 keV (17%). [ 48 ] : 64   For imaging, multiple gamma camera energy windows are used, typically centred around 93 and 184 keV or 93, 184, and 296 keV. [ 24 ]


Gallium-68 , which has a 68 minutes half-life, is produced in a  gallium-68 generator  by decay of  germanium-68  with a 271 day half-life or by the irradiation of  zinc-68  through a low energy cyclotron. Use of a generator means a supply of  68 Ga can be produced easily with minimal infrastructure, for example at sites without a  cyclotron , commonly used to produce other PET isotopes.
It decays by  positron emission  and  electron capture  into zinc-68. [ 49 ]  Maximum energy of positron emission is at 1.9 MeV. [ 48 ] : 65


The  history of radiation therapy  or  radiotherapy  can be traced back to experiments made soon after the discovery of  X-rays  (1895), when it was shown that exposure to  radiation  produced cutaneous  burns . Influenced by  electrotherapy  and  escharotics —the medical application of caustic substances—doctors began using radiation to treat growths and lesions produced by diseases such as  lupus ,  basal cell carcinoma , and  epithelioma . [ 1 ]  Radiation was generally believed to have bactericidal properties, so when  radium  was discovered, in addition to treatments similar to those used with x-rays, it was also used as an additive to medical treatments for diseases such as  tuberculosis  where there were resistant  bacilli . [ 2 ] [ 3 ]


Additionally, because radiation was found to exist in hot spring waters which were reputed for their curative powers, it was marketed as a  wonder cure  for all sorts of ailments in  patent medicine  and  quack  cures. It was believed by medical science that small doses of radiation would cause no harm and the harmful effects of large doses were temporary. [ 4 ]


The widespread use of radium in medicine ended when it was discovered that physical tolerance was lower than expected and exposure caused long term cell damage that could appear in  carcinoma  up to 40 years after treatment. [ 5 ]  The use of radiation continues today as a treatment for cancer in  radiation therapy .


The  imaging  properties of x-rays were discovered, their practical uses for research and diagnostics were immediately apparent, and soon their use spread in the medical field. X-rays were used to diagnose bone fractures, heart disease, and phthisis. Inventive procedures for different diagnostic purposes were created, such as filling digestive cavities with  bismuth , which allowed them to be seen through tissue and bone. [ 6 ]


During early practical work and scientific investigation, experimenters noticed that prolonged exposure to x-rays created inflammation and, more rarely, tissue damage on the skin. The biological effect attracted the interest of  Léopold Freund  and  Eduard Schiff , who, only a month or two after Röntgen's announcement, suggested they be used in the treatment of disease. [ 7 ]  At approximately the same time,  Emil Grubbe , of Chicago was possibly the first American physician to use x-rays to treat cancer, beginning in 1896, began experimenting in Chicago with medical uses of x-rays. [ 8 ]   Escharotics  by this time had already been used to treat skin malignancies through caustic burns, and  electrotherapy  had also been experimented with, in the aim to stimulate the skin tissue. [ citation needed ]


The first attempted x-ray treatment was by  Victor Despeignes , a French physician who used them on a patient with stomach cancer. In 1896, he published a paper with the results: a week-long treatment was followed by a diminution of pain and reduction in the size of the tumor, though the case was ultimately fatal. The results were inconclusive, because the patient was concurrently being given other treatments. [ 9 ]  Freund's first experiment was a tragic failure; he applied x-rays to a  naevus  in order to induce  epilation  and a deep ulcer resulted, which resisted further treatment by radiation. The first successful treatment was by Schiff, working with Freund, in a case of  lupus vulgaris .  A year later, in 1897, the two published a report of their success and this provoked further experimentation in x-ray therapies. [ 10 ]  Thereafter they did a successful treatment of  lupus erythematosus  in 1898. The lesion took a common form of a 'butterfly-patch' which appeared on both sides of the face, and Schiff applied the irradiation to one side only, in order to compare the effects. [ 11 ]


Within a few months, scientific journals were swamped with accounts of the successful treatment of different types of skin tissue malignancies with x-rays. In Sweden,  Thor Stenbeck  published results of the first successful treatments of  rodent ulcer  and  epithelioma  in 1899, later that year confirmed by  Tage Sjögren . [ 12 ]  Soon afterwards, their findings were confirmed by a number of other physicians. [ 13 ]


The nature of the active agent in therapeutic treatment was still unknown, and subject to wide dispute. Freund and Schiff believed it to because of electrical discharge,  Nikola Tesla  argued they were because of the  ozone  generated by the x-rays, while others argued that it was the x-rays themselves. Tesla's position was soon refuted, and only the other two theories remained. In 1900,  Robert Kienböck  produced a study based on a series of experiments that demonstrated that it was the x-rays themselves. Studies published in 1899 and 1900 suggested that the rays varied in penetration according to the degree of vacuum in the tube. [ 14 ]


Niels Finsen , a Faroese-Danish physician, had by that time already pursued interest in the biological effects of light. He published a paper,  Om Lysets Indvirkninger paa Huden  ("On the effects of light on the skin") in 1893. Inspired by the discovery that x-rays could have therapeutic effects, he extended his research to examine directed light rays. In 1896, he published a paper on his findings,  Om Anvendelse i Medicinen af koncentrerede kemiske Lysstraaler  ("The use of concentrated chemical light rays in medicine"). Finsen discovered that lupus was amenable to treatment by  ultraviolet  rays when separated out by a system of  quartz  crystals, and thereafter created a lamp to sift out the rays. The so-called  Finsen lamp  became widely used in for  phototherapy , and derivatives of it became used when experimenting with other types of radiotherapy. [ 15 ]  Modifications were made to Finsen's original design, and it found its most common forms in the  Finsen-Reyn lamp  and  Finsen-Lomholt lamp  .


By 1905, it was estimated that fully 50 percent of the cases of lupus were successfully healed by Finsen's methods. [ 15 ]  Finsen was soon awarded a  Nobel Prize  for his research.


From initial therapeutic experiments, a new field of x-ray therapy was born, referred to as  röntgenotherapy  after  Wilhelm Röntgen , the discoverer of x-rays. It was still unclear how the x-rays acted on the skin; however, it was generally agreed upon that the area affected was killed and either discharged or absorbed. [ 17 ]


By 1900, there were four well established classes of problems that were treated by x-ray, based on a set of five classes initially outlined by Freund:  1.  in hypertrichosis, for the removal of unwanted hair;  2.  in the treatment of disease of hair and hair follicles in which it was necessary to remove hair;  3.  in the treatment of inflammatory affections on the skin like eczema and acne;  4.  and in the treatment of malignant affections on the skin in cases like lupus and epithelioma. [ 18 ] [ 19 ]


Additionally, x-rays were successfully applied to other appearances of  carcinoma , trials were done in treating  leukemia , and because of the supposed bactericidal properties, there were suggestions it could be used in diseases such as tuberculosis. Experiments were also done using x-rays to treat  epilepsy , which had previously also experimentally been treated with electrical currents. [ 20 ]


Because of the excitement over the new treatment, literature about the therapeutic effects of x-rays often exaggerated the propensity to cure different diseases. Reports of the fact that in some cases treatment worsened some of the patients' conditions were ignored in favor of hopeful optimism.  Henry G. Piffard  referred to these practitioners as "radiomaniacs" and "radiografters". It was found that x-rays were only capable of producing a cure in certain cases of the basal cell type of epithelioma and exceedingly unreliable in malignant cancer, not making it a suitable replacement for surgery. In many cases of treatment, the cancer recurred after a period of time. X-ray experiments in pulmonary tuberculosis proved useless. Aside from the medical profession losing faith in the ability of x-ray therapy, the public increasingly viewed it as a dangerous type of treatment. This resulted in a period of pessimism about the use of x-rays, which lasted from about 1905 to 1910 or 1912. [ 21 ]


Soon after the discovery of  radium  in 1898 by Pierre and  Marie Curie , there was speculation in whether the radiation could be used for therapy in the same way as that from x-rays. The physiological effect of radium was first observed in 1900 by  Otto Walkhoff , [ 23 ]  and later confirmed by what famously known as the "Becquerel burn". In 1901,  Henri Becquerel  had placed a tube of radium in a waistcoat pocket where it had remained for several hours; a week or two after which there was severe inflammation of his skin underneath where the radium had been kept.  Ernest Besnier , a dermatologist, examined the skin and expressed the opinion that it was due to the radium, leading to experiments by Curie which confirmed it. Besnier suggested the use of radium for therapy along the same purposes as x-rays and ultraviolet rays.


Becquerel for this purpose loaned some radium to  Henri-Alexandre Danlos  of the  hôpital St. Louis  in Paris in 1901. [ 24 ]  Danlos successfully treated a few cases of lupus with an admixture of  radium  and  barium chloride . Further trials of radium therapy began, though at a much slower pace than did those using x-rays because radium was expensive and difficult to obtain.


Radium was soon seen as a way to treat disorders that were not affected enough by x-ray treatment because it could be applied in a multitude of ways in which x-rays could not. [ 15 ]  Different methods of applying radium had been tested, which fell into two categories: the use of radium emanation (now referred to as  radon ), and the use of radium salts.


One method using emanation was through inhalation, where it was mixed with air. Radium inhalation had been most studied in Germany, where regular inhalation institutes were established, and the goal was to target the lungs. That was done either to treat lung diseases, like tuberculosis, or to be absorbed through the surface of the lung to the blood, where it could circulate through the body. It was claimed that the beneficial effects produced by radium water baths were the result of inhalation of the vapors. [ 27 ]


Another method of treatment was to condense the emanation at liquid air temperature on substances such as vasoline, glycerine, and lanoline, to apply externally to the part affected; or on quinine, bismuth, subnitrate, and arsenic, to be consumed or applied internally. [ 28 ]


Radium emanation was also passed into glass or metal tubes or flat glass-tight applicators and applied in the same way as radium tubes. In other cases was also deposited on metal points or flat surfaces of metal using electrical devices, which had the same level of radioactivity as the parent radium, but lasted a shorter duration. One way of treatment was to then drive the deposits of radioactive material into tissue using galvanic current. It was also a method of applying radium emanation to a specially designed applicator constructed to suit the needs of the patient, who could later take it home. [ 29 ]


Dilute solutions of radium salts were also made, meant to be used internally. Patients would be prescribed regular dosages. More rarely, the salts were also suspended in liquids to be injected in subcutaneous treatments, which could be applied locally to affected tissues. That was considered the most expensive method, because the radium used was irreparably lost. [ 28 ]


As with radium emanation, solutions of free radium salts were also placed in tubes; in this case, the tubes were made from platinum. In metal tubes, the radium could be employed in a number of ways: externally; to the interior of the body in places like the mouth, nose, esophagus, rectum and vagina; and into the substance of a tumor through incisions. [ 29 ]


In 1903, the discoverer of the electron,  J. J. Thomson , wrote a letter to the journal  Nature  in which he detailed his discovery of the presence of radioactivity in well water. Soon after, others found that the waters in many of the world's most famous health springs were also radioactive. This radioactivity is due to the presence of radium emanation produced by the radium that is present in the ground through which the waters flow. In 1904,  Nature  published a study on the natural radioactivity of different mineral waters. [ 30 ]


Inspired by this, using preparations of radium salts in bath water was suggested as a way for patients to be treated at home, as the radio-activity in the bathwater was permanent. [ 31 ]  Radium baths became used experimentally to treat  arthritis ,  gout , and  neuralgias .


X-rays and radium were noted by physicians to have different advantages in different cases. The most marked effects produced with radium therapy were with lupus, ulcerous growths, and  keloid , particularly because they could be applied more specifically to tissues than with x-rays. [ 32 ]  Radium was generally to be preferred when a localized reaction was desired, while for x-rays when a large area needed to be treated. [ 33 ]  Radium was also believed to be bactericidal, while x-rays were not. Because they could not be applied locally, x-rays were also found to have worse cosmetic effects than radium when treating malignancies. In certain cases, a combination of x-ray and radium therapy was suggested. In many skin diseases, the ulcers would be treated with radium and the surrounding areas with x-rays so it would positively affect the lymphatic systems. [ 34 ]


After using radium in the surgical treatment of tuberculosis, researchers including  Béla Augustin  and  A. de Szendeffy  soon developed a treatment using radioactive methyholated iodine, which was patented under the name  dioradin  (formed from "iodine and radium") in 1911. Application of this treatment was referred to as  iodo-radium therapy , and involved injecting dioradin intramuscularly. It seemed promising to the developers, because in several cases, fever and  hemoptysis  had disappeared. [ 3 ]  Inhalation of iodine alone had been an experimental treatment for tuberculosis in France between 1830 and 1870. [ 35 ]


Widespread commercial exploitation of radium only began in 1913, by which time more efficient methods of extracting radium from  pitchblende  had been discovered [ 37 ] [ 38 ]  and the mining of radium had taken off. [ 39 ]


The radium commonly used in bath salts, waters, and muds was in low-grade preparations, due to the expense, and their usefulness in curative solutions was questioned, since it had been agreed upon by physicians that radium could only be used successfully in high doses. [ 40 ]  It was believed that even radiation emanation at higher doses than were useful would cause no harm, because the radioactive deposits were found to have been absorbed and released in urine and waste within a period of three hours. [ 4 ]


Radium emanation activators , apparatuses that would apply radium emanation to water, started being produced and marketed. Scientifically constructed emanators were sold to hospitals, universities, and independent researchers. Certain companies advertised that they would only give them out to others on a medical prescription [ 4 ]  and would guarantee the strength of radium in each dose.


Many products which imitated emanation activators were more broadly marketed to the public. One such product was the  Revigator , a "radioactive water crock."  A dispensing jar made of radium-containing ore, the idea was that radon produced by the ore would dissolve in the water overnight. It was advertised:  "Fill jar every night. Drink freely ... when thirsty and upon arising and retiring, average six or more glasses daily."  The  American Medical Association  (AMA) was concerned that the public was being fleeced by charlatans. In response, the AMA established guidelines (in effect from 1916 to 1929) that emanators seeking AMA approval had to generate more than 2  μ Ci  (74  k Bq ) of radon per liter of water in a 24-hour period. Most devices on the market, including the  Revigator , did not meet that standard. [ 41 ]


Many other  quack  cures and  patent medicines  were sold on the market.  Radithor , a solution of radium salts, was claimed by its developer  William J. A. Bailey  to have curative properties. Many brands of toothpaste were laced with radium that was claimed to make teeth shine whiter, such as  Doramad Radioactive Toothpaste . Ostensibly, this would be because the radium would kill the bacteria in a person's mouth. One item, called "Degnen's Radio-Active Eye Applicator" manufactured by the Radium Appliance Company of Los Angeles, California, was sold as a treatment for  myopia ,  hypermetropia , and  presbyopia . Face creams and powders were sold, with names like 'Revigorette' and 'Tho-radia'. It was also sold as a supplement to smoking cigarettes. Companies also marked radioactive pads and compresses for the treatment of illnesses. [ 42 ]


In light of the supposed curative properties of radioactivity, a spa was opened up in  Joachimsthal , the place at which Madame Curie gathered some of her original samples of radium from spring waters. Radon inhalation rooms were set up, where air tubes carried the gas up from a processing tank in the basement; the visitor would then use it through an inhalation apparatus. Baths were set up which were also irradiated, and irradiated air was also filtered through a trumpet-like pipe for inhalation. [ 5 ]


Concerns about radium were brought up before the  United States Senate  by California Senator  John D. Works  as early as 1915. In a floor speech he quoted letters from doctors asking about the efficacy of the products that were marketed. He stressed that radiation had the effect of making many cancers worse, many doctors thought the belief that radium could be used to cure cancers at that stage of the development of therapy was a "delusion"—one doctor quoted cited a failure-to-success rate of 100 to 1—and the effects of radium water were undemonstrated. [ 43 ]


Around the start of the 1920s, new public health concerns were sparked by the deaths of factory workers at a  radioluminescent  watch factory. In 1932, a well-known industrialist,  Eben Byers  died of radiation poisoning from the use of  Radithor , a radium water guaranteed by the manufacturer to contain 2 μ Ci  of radium. [ 41 ]  Cases sprung up of the development of carcinoma in patients who had used conventional radium therapy up to 40 years after the original treatments. [ 5 ]


Robley D. Evans made the first measurements of exhaled radon and radium excretion from a former dial painter in 1933. At  MIT  he gathered dependable body content measurements from 27 dial painters. This information was used in 1941 by the  National Bureau of Standards  to establish the  tolerance level  for radium of 0.1  μ Ci (3.7  k Bq ). [ 44 ]


At the International Congress of Oncology in Paris in 1922,  Henri Coutard , a French radiologist working with the  Institut Curie , presented evidence that laryngeal cancer could be treated without disastrous side-effects. Coutard was inspired by the observations of  Claudius Regaud , who found that a single dose of x-rays enough to produce severe skin damage and tissue destruction in a rabbit, if administered in fractions, over a course of days, would sterilize the rabbit but have no effect on subcutaneous tissues. [ 45 ]


By 1934, Coutard had developed a protracted, fractionated process that remains the basis for current radiation therapy. [ 46 ]  Coutard's dosage and fractionation were designed to create a severe but recoverable acute mucosal reaction. Unlike previous physicians, who believed that cancerous cells were more affected by radiation, he assumed that the population of cancerous cells had the same sensitivity for regeneration as normal cells. [ 47 ]  Coutard reported a 23% cure rate in the treatment of head and neck cancer. [ 48 ]  In 1935, hospitals everywhere began following his treatment plan. [ 47 ]


"Radiation therapy" defined as the utilization of electromagnetic or particle radiation in medical therapy has 3 main branches, including  external beam radiation therapy  (teletherapy), locoregional ablative therapy (such as brachytherapy (sealed source radiation therapy), selective internal radiotherapy (SIRT), radiofrequency ablation, microwave ablation, and optical therapy), and systemic therapy (i.e. radiopharmaceutical therapy, such as radioligand therapy and unsealed source therapy)). There are three branches of radiology dealing with these three therapeutic domains: Radiation Oncology (teletherapy and brachytherapy), Interventional Radiology / Interventional Oncology (selective internal radiation therapy (SIRT), locoregional ablative therapy using RF ablation and microwave ablation), and Nuclear Radiology / Nuclear Medicine (using radiopharmaceutical therapy (RPT) and systemic unsealed sources).


Particle therapy  is a special case of "radiation therapy" in which "emitted atomic particles" (such as electrons, protons, or neutrons) are used for energy delivery in therapy. Particle therapy is heavily used in Nuclear Radiology / Nuclear Medicine (radiopharmaceutical therapeutic agents are based on alpha particles, beta particles, or auger electrons), and to some extent in Radiation Oncology (external electron therapy and recent emerging modalities for external proton therapy). Nuclear Radiology / Nuclear Medicine specializes in the internal delivery of particle therapy whereas Radiation Oncology specializes in the external and locoregional delivery of particle therapy.


Intraoperative radiation therapy or  IORT  is a special type of radiation therapy that is delivered immediately after surgical removal of cancer. This method has been employed in breast cancer (TARGeted Intra-operative radiation Therapy or  TARGIT ), brain tumors, and rectal cancers.


Radioactive iodine, which has been used to treat thyroid diseases since 1941, survives today primarily in the treatment of  thyrotoxicosis  (hyperthyroidism) and some types of thyroid cancer that absorb iodine. Treatment involves the important iodine isotope  iodine-131  ( 131 I), often simply called "radioiodine" (though technically all  radioisotopes  of iodine are radioiodines; see  isotopes of iodine ).


The  Imaging and  Radiation Oncology Core (IROC)  is a center for the evaluation of data produced by  clinical trials  funded by the  National Cancer Institute , as part of the  National Clinical Trials Network  "to provide integrated radiation oncology and diagnostic imaging quality control programs... thereby assuring high quality data for clinical trials designed to improve the clinical outcomes for cancer patients worldwide." [ 1 ] [ 2 ]


There are currently six centers: [ 3 ]


IROC Houston QA Center, at the  MD Anderson Cancer Center


IROC Ohio QA Center, at  Ohio State University Wexner Medical Center   and James Comprehensive Cancer Center.


IROC Rhode Island QA Center in Lincoln, Rhode Island, administered by the  University of Massachusetts Medical School


IROC Philadelphia (RT) QA Center, at the ACR Research center in Philadelphia,


IROC Philadelphia (Imaging) QA Center, at the ACR Research center in Philadelphia,


IROC St Louis QA Center at  Washington University School of Medicine


The history of the Rhode Island Center (previously known as QARC) goes back to the late 1970s when  Rhode Island Hospital  was conducting RT QA reviews of  leukemia -based protocols for the  CALGB , which is one of the major NCI-sponsored cooperative groups. Other cooperative groups like the  Pediatric Oncology Group  and the  Children's Cancer Study Group  decided to use the center's quality control. QARC began to seek funding from the NCI in order to manage the large influx of data, and received its first grant in  1980. [ 4 ]  Sixteen years later, in 1996, QARC switched its affiliation from  Brown Medical School  to the  University of Massachusetts Medical School  (UMMS). By late 2003, it moved from the  Roger Williams Medical Center   to offices in  Federal Hill, Providence, Rhode Island ; in August 2010, it relocated to its current site in  Lincoln, Rhode Island .


The  indium white blood cell scan  is a  nuclear medicine  procedure in which  white blood cells  (mostly  neutrophils ) are removed from the patient, tagged with the radioisotope  Indium -111, and then injected intravenously into the patient. The tagged leukocytes subsequently localize to areas of relatively new infection. The study is particularly helpful in differentiating conditions such as  osteomyelitis  from  decubitus ulcers  for assessment of route and duration of  antibiotic  therapy. [ 1 ] [ 2 ]


In imaging of infections, the  gallium scan  has a sensitivity advantage over the indium white blood cell scan in imaging  osteomyelitis  (bone infection [ 3 ] ) of the spine, lung infections and inflammation, and in detecting chronic infections. In part, this is because gallium binds to neutrophil membranes, even after neutrophil death, whereas localization of neutrophils labeled with indium requires them to be in relatively good functional order. However, indium leukocyte imaging is better at localizing acute (i.e., new) infections, where live neutrophils are still rapidly and actively localizing to the infection, for imaging for osteomyelitis that does not involve the spine, and for locating abdominal and pelvic infections.


Both the gallium scan and indium-111 white blood cell imaging may be used to image  fever of unknown origin  (elevated temperature without an explanation). However, the indium leukocyte scan will localize only to the approximately 25% of such cases which are caused by acute infections, while gallium is more broadly sensitive, localizing to other sources of fever, such as chronic infections and tumors. Gallium may be a better choice for spleen study because gallium does not normally accumulate in the spleen.


Intraoperative radiation therapy  (IORT) is  radiation therapy  that is administered during surgery directly in the operating room (hence  intraoperative ).


Usually  therapeutic  levels of radiation are delivered to the  tumor bed  while the area is exposed during  surgery . IORT is typically a component in the multidisciplinary treatment of locally advanced and recurrent  cancer , in combination with external beam radiation, surgery, and  chemotherapy . As a growing trend in recent years, IORT can also be used in earlier stage cancers such as prostate and  breast cancer .


IORT was found to be useful and feasible in the multidisciplinary management of many solid tumors but further studies are needed to determine the benefit more precisely. [ 1 ]  Single-institution experiences have suggested a role of IORT e.g. in brain tumors and cerebral metastases, locally advanced and recurrent rectal cancer, skin cancer, retroperitoneal sarcoma, pancreatic cancer, and selected gynaecologic and genitourinary malignancies.  For local recurrences, irradiation with IORT is, besides brachytherapy, the only radiotherapeutic option if repeated EBRT is no longer possible. Generally, the normal tissue tolerance does not allow a second full-dose course of EBRT, even after years. [ 2 ] [ 3 ]


On 25 July 2014, the UK National Institute for Health and Care Excellence (NICE) gave provisional recommendation for the use of TARGIT IORT with Intrabeam in the UK National Health Service. [ 4 ]  The 2015 update of guidelines of the Association of Gynecological Oncology (AGO), an autonomous community of the German Society of Gynecology and Obstetrics (DGGG) and the German Cancer Society includes TARGIT IORT during lumpectomy as a recommended option for women with a T1, Grade 1 or 2, ER positive breast cancer. [ 5 ]


The rationale for IORT is to deliver a high dose of radiation precisely to the targeted area with minimal exposure of surrounding tissues which are displaced or shielded during the IORT. Conventional radiation techniques such as external beam radiotherapy (EBRT) following surgical removal of the tumor have several drawbacks: The tumor bed where the highest dose should be applied is frequently missed due to the complex localization of the wound cavity even when modern radiotherapy planning is used. Additionally, the usual delay between the surgical removal of the tumor and EBRT may allow a repopulation of the tumor cells. These potentially harmful effects can be avoided by delivering the radiation more precisely to the targeted tissues leading to immediate sterilization of residual tumor cells. Another aspect is that wound fluid has a stimulating effect on tumor cells. IORT was found to inhibit the stimulating effects of wound fluid. [ 6 ]


Several methods are used to deliver IORT. IORT can be delivered using electron beams  (electron IORT) , orthovoltage (250–300 kV) X-rays (X-ray IORT), high-dose-rate brachytherapy (HDR-IORT), or low-energy (50 kV) x-rays (low-energy IORT).


While IORT was first used in clinical practice in 1905, [ 7 ] [ 8 ]  the modern era of IORT began with the introduction of electron IORT in the mid-1960s by transporting patients from the OR after the tumor was removed to the radiation department to receive their electron IORT. [ 9 ] [ 10 ]   Electron IORT has the advantages of being able to carefully control the depth of radiation penetration while providing a very uniform dose to the tumor bed.  Applied with energies in the range of 3 MeV to 12 MeV, electron IORT can treat to depths of up to 4 cm over areas as large as 300 cm² (i.e. a 10 cm diameter circle) and takes only 1–3 minutes to deliver the prescribed radiation dose.  A few hospitals built shielded operation rooms in which a conventional linear accelerator was installed to deliver the IORT radiation.  This eliminated the complex logistics involved with patient transportation, but was so costly that only a few hospitals were able to use this approach.  The breakthrough came in 1997, with the introduction of a miniaturized, self-shielded, mobile linear accelerator (Mobetron, IntraOp Corporation, US) [ 11 ]  and a mobile but unshielded linear accelerator (Novac, Liac–SIT, Italy). More than 75,000 patients have been treated with electron IORT, almost half of them since the introduction of mobile electron IORT technology.


Early practitioners of IORT treated primarily abdominal malignancies using superficial X-rays (75–125 kV) and later orthovoltage x-rays (up to 300 kV in energy) prior to the advent of technology that enabled high-energy electrons. For the first 75 years, X-ray IORT was used mostly for palliation, but there were a few anecdotal reports of long-term survivors.  In the early 1980s, when the use of electron IORT was increasing and showed promising results for certain indications, a handful of hospitals installed othovoltage units in lightly shielded ORs to see if this lower cost approach could achieve comparable results to that of electron IORT.  This approach was less costly than building a shielded OR for an electron IORT unit and eliminated the logistics involved with patient transportation.  However, it had a number of problems that limited its appeal.  X-ray IORT has a poor uniformity of dose as a function of depth of penetration, the radiation does not stop at a pre-defined depth but continues to deposit radiation to underlying structures, and can do damage to boney structures if too high a dose is delivered.  Despite its long use (since the 1930s), fewer than 1000 patients have been treated with this approach, and it is no longer offered at most centers. [ 12 ]


This technique was developed in the late 1980s in an attempt to combine the dosimetric advantages of high-dose rate brachytherapy with the challenges of treating some complex anatomic surfaces with IORT. It has the advantage of being lower cost than dedicated electron IORT systems, since many radiation centers already have an HDR system that can be transported to the OR when HDR-IORT is needed.  HDR-IORT can also treat very large and convoluted surfaces. However, it does require a shielded OR or a shielded room in the OR complex to deliver the HDR-IORT. [ 13 ]  The depth of penetration is very limited, typically either ½ cm to 1 cm depth, sometimes requiring extensive surgery due to the limited penetration of the radiation. Treatments tend to be 40 minutes or longer, resulting in greater OR time, more anesthesia and greater blood loss when compared to electron IORT.  There are about 10 to 20 active centers using HDR-IORT for locally advanced and recurrent disease, and approximately 2000 patients have received this treatment, mostly for colorectal cancer, head and neck cancer, and gynecologic cancer.


Intrabeam, [ 14 ]  ( Carl Zeiss AG , Germany) received FDA and CE approval in 1999 and is a miniature mobile X-ray source which emits low-energy X-ray radiation (max. 50 kV) in isotropic distribution. Due to the higher ionization density caused by soft X-ray radiation in the tissue, the  relative biological effectiveness  (RBE) of low-energy X-rays on tumor cells is higher when compared to high-energy X-rays or gamma rays which are delivered by linear accelerators. [ 15 ]  The radiation which is produced by low-energy mobile radiation systems has a limited range. For this reason, conventional walls are regarded sufficient to stop the radiation scatter produced in the operating room and no extra measures for radiation protection are necessary. This makes IORT accessible for more hospitals.  Targeted intra-operative radiotherapy  is a low-energy IORT technique. Evaluation of the long-term outcomes in patients who were treated with TARGIT-IORT for breast cancer confirmed that it is as effective as whole breast  external beam radiotherapy  in controlling cancer, and also reduces deaths from other causes [ 16 ]  as shown in a large international randomised clinical trial published in the  British Medical Journal . [ 17 ]


Iodine-125  ( 125 I) is a  radioisotope  of  iodine  which has uses in  biological assays ,  nuclear medicine  imaging and in  radiation therapy  as brachytherapy to treat a number of conditions, including  prostate cancer ,  uveal melanomas , and  brain tumors . It is the second longest-lived radioisotope of iodine, after  iodine-129 .


Its  half-life  is 59.392 days and it decays by  electron capture  to an excited state of  tellurium-125 . This state is not the metastable  125m Te, but rather a lower energy state that decays immediately by  gamma decay  with a maximum energy of 35  keV . Some of the excess energy of the excited  125 Te may be  internally converted  ejected electrons (also at 35 keV), or to  x-rays  (from electron  bremsstrahlung ), and also a total of 21  Auger electrons , which are produced at the low energies of 50 to 500 electron volts. [ 3 ]  Eventually, stable ground state  125 Te is produced as the final decay product.


In medical applications, the internal conversion and Auger electrons cause little damage outside the cell which contains the isotope atom. The X-rays and gamma rays are of low enough energy to deliver a higher radiation dose selectively to nearby tissues, in "permanent" brachytherapy where the isotope capsules are left in place ( 125 I competes with  palladium-103  in such uses). [ 4 ]


Because of its relatively long half-life and emission of low-energy photons which can be detected by  gamma-counter   crystal detectors ,  125 I is a preferred isotope for  tagging   antibodies  in  radioimmunoassay  and other gamma-counting procedures involving  proteins  outside the body. The same properties of the isotope make it useful for brachytherapy, and for certain nuclear medicine scanning procedures, in which it is attached to proteins ( albumin  or  fibrinogen ), and where a half-life longer than that provided by  123 I is required for diagnostic or lab tests lasting several days.


Iodine-125 can be used in  scanning/imaging  the  thyroid , but iodine-123 is preferred for this purpose, due to better  radiation penetration  and shorter half-life (13 hours).  125 I is useful for  glomerular filtration rate  (GFR) testing in the diagnosis or monitoring of patients with  kidney disease . Iodine-125 is used  therapeutically  in  brachytherapy  treatments of  tumors . For  radiotherapy   ablation  of tissues that absorb iodine (such as the thyroid), or that absorb an iodine-containing  radiopharmaceutical , the  beta-emitter   iodine-131  is the preferred isotope.


When studying  plant immunity ,  125 I is used as the  radiolabel  in tracking  ligands  to determine which  plant pattern recognition receptors  (PRRs) they bind to. [ 5 ]


125 I is produced by the  electron capture  decay of  125 Xe , which is an artificial isotope of  xenon , itself created by  neutron capture  of near-stable  124 Xe  (it undergoes  double electron capture  with a half life orders of magnitude larger than the age of the universe), which makes up around 0.1% of naturally occurring xenon. Because of the artificial production route of  125 I and its short half-life, its  natural abundance  on Earth is effectively zero.


125 I is a reactor-produced radionuclide and is available in large quantities. Its production involves the two following  nuclear reactions :


The irradiation target is the  primordial nuclide   124 Xe, which is the target isotope for making  125 I by  neutron capture . It is loaded into irradiation capsules of the zirconium alloy  zircaloy-2  (a  corrosion  resisting  alloy  transparent to  neutrons ) to a pressure of about  100  bar   (~ 100  atm ) . Upon irradiation with  slow neutrons  in a  nuclear reactor , several  radioisotopes of xenon  are produced. However, only the decay of  125 Xe leads to a radioiodine:  125 I. The other xenon radioisotopes decay either to stable  xenon , or to various  caesium isotopes , some of them radioactive (a.o., the long-lived  135 Cs  ( t ½  = 1.33 Ma) and  137 Cs  ( t ½  = 30 a)).


Long  irradiation  times are disadvantageous. Iodine-125 itself has a  neutron capture   cross section  of 900  barns , and consequently during a long irradiation, part of the  125 I formed will be converted to  126 I, a  beta-emitter  and  positron-emitter  with a  half-life  of 12.93 days, [ 1 ]  which is not medically useful. In practice, the most useful irradiation time in the reactor amounts to a few days. Thereafter, the irradiated gas is allowed to decay for three or four days to eliminate short-lived unwanted radioisotopes, and to allow the newly produced xenon-125 ( t ½  = 17 hours) to decay to iodine-125.


To isolate radio-iodine, the irradiated capsule is first cooled at low temperature (to  condense  the free iodine gas onto the capsule inner wall) and the remaining Xe gas is vented in a controlled way and recovered for further use. The inner walls of the capsule are then rinsed with a dilute  NaOH  solution to collect iodine as  soluble   iodide  (I − ) and  hypoiodite  (IO − ), according to the standard  disproportionation  reaction of  halogens  in  alkaline  solution. Any  caesium  atom present immediately  oxidizes  and passes into the water as Cs + . In order to eliminate any long-lived  135 Cs and  137 Cs which may be present in small amounts, the solution is passed through a  cation-exchange  column, which exchanges Cs +  for another non-radioactive  cation  (e.g., Na + ). The radioiodine (as  anion  I −  or IO − ) remains in solution as a mixture iodide/hypoiodite.


Iodine-125 is commercially available in dilute  NaOH  solution as  125 I-iodide (or the  hypohalite  sodium  hypoiodite , NaIO). The radioactive concentration lies at 4 to  11 GBq/mL  and the specific radioactivity is  > 75 GBq/μmol   (7.5 × 10 16  Bq/mol) . The chemical and radiochemical purity is high. The radionuclidic purity is also high; some  126 I  ( t 1/2  = 12.93 d) [ 1 ]  is unavoidable due to the  neutron capture  noted above. The  126 I tolerable content (which is set by the unwanted isotope interfering with  dose calculations  in  brachytherapy ) lies at about  0.2 atom %  ( atom fraction ) of the total iodine (the rest being  125 I).


As of October 2019, there were two producers of iodine-125, the  McMaster Nuclear Reactor  in  Hamilton ,  Ontario , Canada; and a VVR-SM research reactor in Uzbekistan. [ 6 ]  The McMaster reactor is presently the largest producer of iodine-125, producing approximately 60 per cent of the global supply in 2018; [ 7 ]  with the remaining global supply produced at the reactor based in Uzbekistan. Annually, the McMaster reactor produces enough iodine-125 to treat approximately 70,000 patients. [ 8 ]


In November 2019, the research reactor in Uzbekistan shut down temporarily in order to facilitate repairs. The temporary shutdown threatened the global supply of the radioisotope by leaving the McMaster reactor as the sole producer of iodine-125 during the period. [ 6 ] [ 8 ]


Prior to 2018, the  National Research Universal  (NRU) reactor at  Chalk River Laboratories  in  Deep River , Ontario, was one of three reactors to produce iodine-125. [ 9 ]  However, on March 31, 2018, the NRU reactor was permanently shut down ahead of its scheduled decommissioning in 2028, as a result of a government order. [ 10 ] [ 11 ]  The Russian nuclear reactor equipped to produce iodine-125, was offline as of December 2019. [ 6 ]


The detailed decay mechanism to form the stable daughter nuclide tellurium-125 is a multi-step process that begins with  electron capture . This is followed by a cascade of  electron relaxation  as the core electron hole moves toward the  valence orbitals . The cascade involves many  Auger transitions , each of which cause the atom to become increasingly  ionized . The electron capture produces a tellurium-125 nucleus in an excited state with a half-life of 1.6 ns, which undergoes  gamma decay  emitting a gamma  photon  or an  internal conversion   electron  at 35.5 keV. A second electron relaxation cascade follows the gamma decay before the nuclide comes to rest.  Throughout the entire process an average of 13.3 electrons are emitted (10.3 of which are  Auger electrons ), most with energies less than 400 eV (79% of yield). [ 12 ]  The internal conversion and Auger electrons from the radioisotope have been found in one study to do little cellular damage, unless the radionuclide is directly incorporated chemically into cellular  DNA , which is not the case for present radiopharmaceuticals which use  125 I as the radioactive label nuclide. [ 13 ]


As with other radioisotopes of iodine, accidental iodine-125 uptake in the body (mostly by the  thyroid  gland) can be blocked by the prompt administration of stable  iodine-127  in the form of an iodide salt. [ 14 ] [ 15 ]   Potassium iodide  (KI) is typically used for this purpose. [ 16 ]


However, unjustified  self-medicated  preventive administration of stable KI is not recommended in order to avoid disturbing the normal  thyroid function . Such a treatment must be carefully dosed and requires an appropriate KI amount  prescribed  by a specialised physician.


Isocenter  in  aerial photography : it is a  point where a line cuts an angle of 90 degree of tier/2. [ clarification needed ]
It is the point on the aerial photo platform that directly falls on a line half-way between the Principal point and the Nadir point.
In  imaging physics  and  radiation oncology , the  isocenter  is termed as the point in space through which the central rays of the radiation beams pass.


In  radiation oncology  there is typically talk of two isocenters:


Radiation isocenter is the point in space through which the central beam of radiation passes whereas the mechanical isocenter is the point where optical beams intersect. The two are closely related but differ in terms of their functionality and working in Space.


Isocenter definition in  Radiotherapy :


The point in space relative to the treatment machine about which various components of the linac rotate. The  gantry  rotation defines
a horizontal axis which cuts a vertical axis defined by the rotation of the treatment couch. The treatment collimators also
rotate about an axis pointing through the isocentre.


The  source to isocenter distance  (SIsoD) can be an important parameter to control in determining patient exposure and image quality in diagnostic  computed tomography  and  fluoroscopy .


Jennifer Clare Jones  is an American  radiation oncologist  and biologist. She is an investigator and head of the translational nanobiology section at the  National Cancer Institute .


Jones completed a M.D. and Ph.D. from  Stanford University . She is a board-certified radiation oncologist specialized training in radiosurgery, with graduate and postdoctoral training in both cancer biology and general immunology. [ 1 ]  Her doctoral advisor was  Dale Umetsu  [ Wikidata ] . Jones' dissertation in 2001 was titled,  Identification of Tapr, a T cell and airway phenotype regulatory locus, and positional cloning of the Tim gene family . [ 2 ]


Jones is a NIH Stadtman Investigator and head of the translational  nanobiology  section at the  National Cancer Institute . [ 3 ]


From 2001 to 2003, Jones positionally cloned the T-cell immunoglobulin mucin (TIM) gene family and demonstrated the genetic association between TIMs and immune response profiles. As a  radiation oncologist , her research is focused on developing immune-based therapies that synergize with radiation to produce optimal  anti-tumor  immune responses. Jones develops improved methods to characterize, sort, and perform functional studies of nanoparticles, and has established a translational EV analysis pipeline, with instrumentation for preparation, analysis, counting, and  cytometric  study of  extracellular vesicles . [ 3 ]


Megavoltage X-rays  are produced by  linear accelerators  ("linacs") operating at  voltages  in excess of 1000  kV  (1 MV) range, and therefore have an  energy  in the  MeV  range. The voltage in this case refers to the voltage used to accelerate electrons in the linear accelerator and indicates the maximum possible energy of the photons which are subsequently produced. [ 1 ]   They are used in medicine in  external beam radiotherapy  to treat  neoplasms ,  cancer  and  tumors .   Beams with a voltage range of 4-25 MV are used to treat deeply buried cancers because  radiation oncologists  find that they penetrate well to deep sites within the body. [ 2 ]   Lower energy x-rays, called  orthovoltage X-rays , are used to treat cancers closer to the surface. [ 3 ]


Megavoltage x-rays are preferred for the treatment of deep lying tumours as they are attenuated less than lower energy photons, and will penetrate further, with a lower skin dose. [ 4 ] [ 5 ] [ 6 ]  Megavoltage X-rays also have lower  relative biological effectiveness  than orthovoltage x-rays. [ 7 ]  These properties help to make megavoltage x-rays the most common beam energies typically used for radiotherapy in modern techniques such as  IMRT . [ 8 ]


The use of megavoltage x-rays for treatment first became widespread with the use of  Cobalt-60 machines  in the 1950s. [ 9 ]  However prior to this other devices had been capable of producing megavoltage radiation, including the 1930s  Van de Graaff generator  and  betatron . [ 10 ] [ 11 ] [ 12 ]


Microwave thermotherapy  is a type of treatment in which  body tissue  is heated by  microwave  irradiation to damage and kill  cancer cells  or to make cancer cells more sensitive to the effects of  radiation  and certain anticancer drugs.


A  monitor unit  ( MU ) is a measure of machine output from a clinical accelerator for  radiation therapy  such as a  linear accelerator  or an  orthovoltage  unit. Monitor units are measured by monitor chambers, which are  ionization chambers  that measure the  dose  delivered by a beam and are built into the treatment head of radiotherapy linear accelerators. [ 1 ]


Linear accelerators are calibrated to give a particular  absorbed dose  under particular conditions, although the definition and measurement configuration may vary among medical clinics. [ 2 ] [ 3 ]


The most common definitions are: [ 4 ]


Some linear accelerators are calibrated using source-to-axis distance (SAD) instead of source-to-surface distance (SSD), and calibration (monitor unit definition) may vary depending on hospital custom.


Early radiotherapy was performed using "constant SSD" treatments, and so the definition of monitor unit was adopted to reflect this calibration geometry.


Modern radiotherapy is performed using  isocentric  treatment  plans , so newer definitions of the monitor unit are based on geometry at the  isocenter  based on the source-to-axis distance (SAD).


Nearly 60% of the reported errors involved a lack of an appropriate independent secondary check of the treatment plan or dose calculation  [ 5 ]


With the development and technological advances, radiotherapy requires that high doses of radiation are delivered to the tumor with increasing precision. According to the recommendations of the International Commission on Radiation Units and Measurements (ICRU) in Publication 24
, [ 6 ]  the delivered dose should not deviate by more than ± 5% of the prescribed dose. More recently, the new ICRU recommendations in Publication 62 [ 7 ]


Commercially available computerized treatment planning systems are often used in radiotherapy services to perform monitoring unit (MU) calculations to deliver the prescribed dose to the patient. As only a part of the total dose uncertainty originates from the calculation process in treatment planning, the tolerance for accuracy of planning systems has to be smaller. [ 8 ] [ 9 ]


Publications on quality assurance in radiotherapy have recommended routine checks of MU calculations through independent manual calculation. This type of verification can also increase confidence in the accuracy of the algorithm and in the  data integrity  of the beams used, in addition to providing an indication of the limitations of the application of conventional dose calculation algorithms used by planning systems. [ 10 ]  Table 1 lists MU calculation software manufacturers.


VMAT


TomoTherapy


CyberKnife


Halcyon


IMRT


A  multileaf collimator  ( MLC ) is a  Collimator  or beam-limiting device that is made of individual "leaves" of a high  atomic numbered  material, usually  tungsten , that can move independently in and out of the path of a  radiotherapy beam  in order to shape it and vary its intensity.


MLCs are used in external beam radiotherapy to provide conformal shaping of beams. Specifically,  conformal radiotherapy  and  Intensity Modulated Radiation Therapy  (IMRT) can be delivered using MLCs.


The MLC has improved rapidly since its inception and the first use of leaves to shape structures in 1965  [ 1 ]  to modern day operation and use. MLCs are now widely used and have become an integral part of any radiotherapy department. MLCs were primarily used for conformal radiotherapy, and have allowed the cost-effective implementation of conformal treatment with significant time saving, [ 2 ]  and also have been adapted for use for IMRT treatments. For conformal radiotherapy the MLC allows conformal shaping of the beam to match the borders of the target tumour. For intensity modulated treatments the leaves of a MLC can be moved across the field to create IMRT distributions (MLCs really provide a  fluence  modulation rather than intensity modulation).


The MLC is an important tool for radiation therapy dose delivery. It was originally used as a surrogate for alloy block field shaping and is now widely used for IMRT. As with any tool used in radiotherapy the MLC must undergo commissioning and quality assurance. Additional commissioning measurements are completed to model a MLC for  treatment planning . Various MLCs are provided by different vendors and they all have unique design features as determined by specifications of design, [ 3 ]  and these differences are quite significant.


This article related to  medical equipment  is a  stub . You can help Wikipedia by  expanding it .


Nanoimpellers  are an experimental technology developed to eliminate some of the harmful effects of  chemotherapy  by facilitating treatment of only specific areas of the body. Nanoimpellers are  nanoscale , light-activated containers filled with  cancer -fighting drugs that only release their contents when hit by a specific type of  laser . [ 1 ]


Nanoimpellers for cancer drug delivery were first demonstrated in 2008. [ 2 ] [ 3 ]  Initial work used  ultraviolet light , however the low penetration in tissue and potential for  toxicity  mean this is not well suited for delivery in patients. [ 1 ]  Later work has shifted to using  near infrared  light and two photon excitation (TPE) to trigger release. [ 4 ] [ 5 ]


Neutron generators  are  neutron source  devices which contain compact  linear particle accelerators  and that produce  neutrons  by fusing  isotopes of hydrogen  together. The  fusion  reactions take place in these devices by accelerating either  deuterium ,  tritium , or a mixture of these two isotopes into a metal  hydride  target which also contains deuterium, tritium or a mixture of these  isotopes . Fusion of deuterium atoms (D + D) results in the formation of a  helium-3  ion and a neutron with a kinetic energy of approximately 2.5  MeV . Fusion of a deuterium and a tritium atom (D + T) results in the formation of a  helium-4  ion and a neutron with a kinetic energy of approximately 14.1 MeV. Neutron generators have applications in medicine, security, and materials analysis. [ 1 ]


The basic concept was first developed by  Ernest Rutherford 's team in the  Cavendish Laboratory  in the early 1930s. Using a linear accelerator driven by a  Cockcroft–Walton generator ,  Mark Oliphant  led an experiment that fired deuterium ions into a deuterium-infused metal foil and noticed that a small number of these particles gave off  alpha particles . This was the first demonstration of nuclear fusion, as well as the first discovery of Helium-3 and tritium, created in these reactions. The introduction of new power sources has continually shrunk the size of these machines, from Oliphant's that filled the corner of the lab, to modern machines that are highly portable. Thousands of such small, relatively inexpensive systems have been built over the past five decades.


While neutron generators do produce fusion reactions, the number of accelerated ions that cause these reactions is very low. It can be easily demonstrated that the energy released by these reactions is many times lower than the energy needed to accelerate the ions, so there is no possibility of these machines being used to produce net  fusion power . A related concept,  colliding beam fusion , attempts to address this issue using two accelerators firing at each other.


Small neutron generators using the deuterium (D, hydrogen-2,  2 H) tritium (T, hydrogen-3,  3 H) fusion reactions are the most common accelerator based (as opposed to radioactive isotopes) neutron sources.  In these systems, neutrons are produced by creating ions of deuterium, tritium, or deuterium and tritium and accelerating these into a hydride target loaded with deuterium, or deuterium and tritium.  The DT reaction is used more than the DD reaction because the yield of the DT reaction is 50–100 times higher than that of the DD reaction.


2 P + 2 N = 17.7 MeV  [19,34 MeV - 1,626 MeV]


D + T → n +  4 He     E n  = 14.1 MeV


D + D -> p + Positron + 3 x Gamma = 2.5 MeV


high beginning energy: 11,4 MeV : D + D → p + Positron + 2 Gamma +  3 He


E n  =  13.91 MeV is right. -> sum: ca. 2.5 MeV


Calculation:
6,8 MeV [Proton-> Hypoproton]+   1,26*1,45 +1,26*0,42 [2,11] MeV   [Hyperneutron  -> Neutron]   +  ~ 2x 2.5 [5] MeV   [Hyperneutron-> Hyperproton]
2x HN Deuterium + high energie => 3 He + Proton + Positron + 2 x Gamma


Neutrons produced by DD and DT reactions are emitted somewhat  anisotropically  from the target, slightly biased in the forward (in the axis of the ion beam) direction. The anisotropy of the neutron emission from DD and DT reactions arises from the fact the reactions are  isotropic  in the  center of momentum coordinate system (COM)  but this isotropy is lost in the transformation from the COM coordinate system to the  laboratory frame of reference . In both frames of reference, the He nuclei recoil in the opposite direction to the emitted neutron consistent with the law of  conservation of momentum .


The gas pressure in the ion source region of the neutron tubes generally ranges between 0.1 and 0.01  mm Hg . The  mean free path  of electrons must be shorter than the discharge space to achieve ionization (lower limit for pressure) while the pressure must be kept low enough to avoid formation of discharges at the high extraction voltages applied between the electrodes. The pressure in the accelerating region, however, has to be much lower, as the mean free path of electrons must be longer to prevent formation of a discharge between the high voltage electrodes. [ 2 ]


The ion accelerator usually consists of several electrodes with cylindrical symmetry, acting as an  einzel lens . The ion beam can thus be focused to a small point at the target. The accelerators typically require power supplies of 100–500 kV. They usually have several stages, with voltage between the stages not exceeding 200 kV to prevent  field emission . [ 2 ]


In comparison with radionuclide neutron sources, neutron tubes can produce much higher  neutron fluxes  and consistent (monochromatic) neutron energy spectra can be obtained. The neutron production rate can also be controlled. [ 2 ]


The central part of a neutron generator is the particle accelerator itself, sometimes called a neutron tube. Neutron tubes have several components including an ion source, ion optic elements, and a beam target; all of these are enclosed within a vacuum-tight enclosure. High voltage insulation between the ion optical elements of the tube is provided by glass and/or ceramic insulators. The neutron tube is, in turn, enclosed in a metal housing, the accelerator head, which is filled with a dielectric medium to insulate the high voltage elements of the tube from the operating area. The accelerator and ion source high voltages are provided by external power supplies. The control console allows the operator to adjust the operating parameters of the neutron tube. The power supplies and control equipment are normally located within 3–10 metres (10–30 ft) of the accelerator head in laboratory instruments, but may be several  kilometers  away in  well logging  instruments.


In comparison with their predecessors, sealed neutron tubes do not require  vacuum pumps  and gas sources for operation. They are therefore more mobile and compact, while also durable and reliable. For example, sealed neutron tubes have replaced radioactive  modulated neutron initiators , in supplying a pulse of neutrons to the imploding core of modern  nuclear weapons .


Examples of neutron tube ideas date as far back as the 1930s, pre-nuclear weapons era, by German scientists filing a 1938 German patent (March 1938, patent #261,156) and obtaining a United States Patent (July 1941, USP #2,251,190); examples of present state of the art are given by developments such as the  Neutristor , [ 3 ]  a mostly solid state device, resembling a computer chip, invented at  Sandia National Laboratories  in Albuquerque NM. [ citation needed ]  Typical sealed designs are used in a pulsed mode [ 4 ]  and can be operated at different output levels, depending on the life from the ion source and loaded targets. [ 5 ]


A good ion source should provide a strong  ion beam  without consuming much of the gas. For hydrogen isotopes, production of atomic ions is favored over molecular ions, as atomic ions have higher neutron yield on collision. The ions generated in the ion source are then extracted by an electric field into the accelerator region, and accelerated towards the target. The gas consumption is chiefly caused by the pressure difference between the ion generating and ion accelerating spaces that has to be maintained. Ion currents of 10 mA at gas consumptions of 40 cm 3 /hour are achievable. [ 2 ]


For a sealed neutron tube, the ideal ion source should use low gas pressure, give high ion current with large proportion of atomic ions, have low gas clean-up, use low power, have high reliability and high lifetime, its construction has to be simple and robust and its maintenance requirements have to be low. [ 2 ]


Gas can be efficiently stored in a replenisher, an electrically heated coil of zirconium wire. Its temperature determines the rate of absorption/desorption of hydrogen by the metal, which regulates the pressure in the enclosure.


The  Penning  source is a low gas pressure,  cold cathode  ion source which utilizes crossed electric and magnetic fields. The ion source anode is at a positive potential, either dc or pulsed, with respect to the source cathode. The ion source voltage is normally between 2 and 7 kilovolts. A magnetic field, oriented parallel to the source axis, is produced by a  permanent magnet . A  plasma  is formed along the axis of the anode which traps electrons which, in turn, ionize gas in the source. The ions are extracted through the exit cathode. Under normal operation, the ion species produced by the Penning source are over 90% molecular ions. This disadvantage is however compensated for by the other advantages of the system.


One of the cathodes is a cup made of  soft iron , enclosing most of the discharge space. The bottom of the cup has a hole through which most of the generated ions are ejected by the magnetic field into the acceleration space. The soft iron shields the acceleration space from the magnetic field, to prevent a breakdown. [ 2 ]


Ions emerging from the exit cathode are accelerated through the potential difference between the exit cathode and the accelerator electrode. The schematic indicates that the exit cathode is at ground potential and the target is at high (negative) potential. This is the case in many sealed tube neutron generators. However, in cases when it is desired to deliver the maximum flux to a sample, it is desirable to operate the neutron tube with the target grounded and the source floating at high (positive) potential. The accelerator voltage is normally between 80 and 180 kilovolts.


The accelerating electrode has the shape of a long hollow cylinder. The ion beam has a slightly diverging angle (about 0.1  radian ). The electrode shape and distance from target can be chosen so the entire target surface is bombarded with ions. Acceleration voltages of up to 200 kV are achievable.


The ions pass through the accelerating electrode and strike the target. When ions strike the target, 2–3 electrons per ion are produced by secondary emission. In order to prevent these secondary electrons from being accelerated back into the ion source, the accelerator electrode is biased negative with respect to the target. This voltage, called the suppressor voltage, must be at least 500 volts and may be as high as a few kilovolts. Loss of suppressor voltage will result in damage, possibly catastrophic, to the neutron tube.


Some neutron tubes incorporate an intermediate electrode, called the focus or extractor electrode, to control the size of the beam spot on the target.  The gas pressure in the source is regulated by heating or cooling the gas reservoir element.


Ions can be created by electrons formed in high-frequency electromagnetic field. The discharge is formed in a tube located between electrodes, or inside a  coil . Over 90% proportion of atomic ions is achievable. [ 2 ]


Input - target for hyperneutron decay detector: e.g. could be tungsten cones in nested pre-cylinder pre-diodes out of wolfrum
The targets used in neutron detector itself are  thin films  of metal such as  titanium ,  scandium , or  zirconium  which are deposited onto a  silver ,  copper  or  molybdenum  substrate. Titanium, scandium, and zirconium form stable chemical compounds called  metal hydrides  when combined with hydrogen or its isotopes. These metal hydrides are made up of two  hydrogen  ( deuterium  or  tritium ) atoms per metal atom and allow the target to have extremely high densities of hydrogen. This is important to maximize the neutron yield of the neutron tube. The gas reservoir element also uses metal hydrides, e.g.  uranium hydride , as the active material.


Titanium is preferred to zirconium as it can withstand higher temperatures (200 °C), and gives higher neutron yield as it captures  deuterons  better than zirconium. The maximum temperature allowed for the target, above which hydrogen isotopes undergo desorption and escape the material, limits the ion current per surface unit of the target; slightly divergent beams are therefore used. A 1 microampere ion beam accelerated at 200 kV to a titanium-tritium target can generate up to 10 8  neutrons per second. The neutron yield is mostly determined by the accelerating voltage and the ion current level. [ 2 ]


An example of a tritium target in use is a 0.2 mm thick silver disc with a 1 micrometer layer of titanium deposited on its surface; the titanium is then saturated with tritium. [ 2 ]


Metals with sufficiently low hydrogen diffusion can be turned into deuterium targets by bombardment of deuterons until the metal is saturated. Gold targets under such condition show four times higher efficiency than titanium. Even better results can be achieved with targets made of a thin film of a high-absorption high-diffusivity metal (e.g. titanium) on a substrate with low hydrogen diffusivity (e.g. silver), as the hydrogen is then concentrated on the top layer and can not diffuse away into the bulk of the material. Using a deuterium-tritium gas mixture, self-replenishing D-T targets can be made. The neutron yield of such targets is lower than of tritium-saturated targets in deuteron beams, but their advantage is much longer lifetime and constant level of neutron production. Self-replenishing targets are also tolerant to high-temperature  bake-out  of the tubes, as their saturation with hydrogen isotopes is performed after the bakeout and tube sealing. [ 2 ]


One approach for generating the high voltage fields needed to accelerate ions in a neutron tube is to use a  pyroelectric crystal .  In April 2005 researchers at  UCLA  demonstrated the use of a thermally cycled  pyroelectric  crystal to generate high electric fields in a neutron generator application.  In February 2006 researchers at  Rensselaer Polytechnic Institute  demonstrated the use of two oppositely poled crystals for this application.  Using these low-tech power supplies it is possible to generate a sufficiently high  electric field  gradient across an accelerating gap to accelerate deuterium ions into a deuterated target to produce the D + D fusion reaction.  These devices are similar in their operating principle to conventional sealed-tube neutron generators which typically use  Cockcroft–Walton  type high voltage power supplies.  The novelty of this approach is in the simplicity of the high voltage source.  Unfortunately, the relatively low accelerating current that pyroelectric crystals can generate, together with the modest pulsing frequencies that can be achieved (a few cycles per minute) limits their near-term application in comparison with today's commercial products (see below).  Also see  pyroelectric fusion . [ 6 ]


In addition to the conventional neutron generator design described above several other approaches exist to use electrical systems for producing neutrons.


Another type of innovative neutron generator is the  inertial electrostatic confinement  fusion device.  This neutron generator avoids using a solid target which will be sputter eroded causing metalization of insulating surfaces. Depletion of the reactant gas within the solid target is also avoided. Far greater operational lifetime is achieved. Originally called a fusor, it was invented by  Philo Farnsworth , the inventor of electronic  television .


Neutron generators find application in semiconductor production industry. They also have use cases in the enrichment of depleted uranium, acceleration of breeder reactors, and activation and excitement of experimental thorium reactors.


In material analysis  neutron activation analysis  is used to determine concentration of different elements in mixed materials such as minerals or ores.
Approximate model of a balancing hyperneutron decay detector with two decay options in normal neutrons and hyperprotons.
These follow-up detectors could be developed to be even more precise.


Oncology Information System  ( OIS ) is a software solution that manages departmental, administrative and clinical activities in  cancer  care. It aggregates information into a complete  oncology -specific  electronic health record  to support medical information management. The OIS allows the capture of patient history information, the documentation of the treatment response,  medical prescription  of the treatment, the storage of patient documentation and the capture of activities for billing purposes. [ 1 ] [ 2 ]


Unlike a  hospital information system  (HIS), which is intended to manage patient records more generally, or  radiological information system  (RIS), intended to track and manage  radiology  requests and workflow, the OIS supports the delivery of integrated care and long-term treatment for cancer patients by collecting data during various phases of treatment, maintaining a history of  treatment fractions ,  screening , prevention, diagnosis, image reviews,  palliative care  and  end-of-life care . An OIS will be designed around the specific requirements of  chemotherapy ,  radiotherapy  and other supportive activities. [ 3 ] [ 4 ]


OIS generally support the following features: [ 1 ]


Orthovoltage X-rays  are produced by  X-ray tubes  operating at  voltages  in the 100–500  kV  range, and therefore the X-rays have a peak  energy  in the 100–500  keV  range. [ 1 ]  Orthovoltage X-rays are sometimes termed  "deep" X-rays  (DXR). [ 2 ]  They cover the upper limit of energies used for diagnostic  radiography , and are used in  external beam radiotherapy  to treat  cancer  and  tumors .  They penetrate tissue to a useful depth of about 4–6 cm. [ 3 ]  This makes them useful for treating  skin , superficial tissues, and ribs, but not for deeper structures such as  lungs  or pelvic organs. [ 4 ]  The relatively low energy of orthovoltage X-rays causes them to interact with matter via different physical mechanisms compared to higher energy  megavoltage X-rays  or radionuclide  γ-rays , increasing their  relative biological effectiveness .  [ 5 ]


The energy and penetrating ability of the X-rays produced by an X-ray tube increases with the  voltage  on the tube.  External beam radiotherapy began around the turn of the 20th century with ordinary diagnostic X-ray tubes, which used voltages below 150 kV. [ 6 ]  Physicians found that these were adequate for treating superficial tumors, but not tumors inside the body. Since these low energy X-rays were mostly absorbed in the first few centimeters of tissue, to deliver a large enough radiation dose to buried tumors would cause severe skin burns. [ 7 ]


Therefore beginning in the 1920s "orthovoltage" 200–500 kV X-ray machines were built. [ 8 ]  These were found to be able to reach shallow tumors, but to treat tumors deep in the body more voltage was needed.   By the 1930s and 1940s  megavoltage X-rays  produced by huge machines with 3–5 million volts on the tube, began to be employed.  With the introduction of  linear accelerators  in the 1970s, which could produce 4–30 MV beams, orthovoltage X-rays are now considered quite shallow. [ 9 ]


In  biochemistry , the  oxygen effect  refers to a tendency for increased  radiosensitivity  of free  living cells  and organisms in the presence of  oxygen  than in  anoxic or hypoxic  conditions, where the  oxygen tension  is less than 1% of  atmospheric pressure  (i.e., <1% of 101.3 kPa, 760 mmHg or 760 torr).


The oxygen effect has particular importance in external beam  radiation therapy  where the killing of  tumour cells  with  photon  and  electron  beams in well oxygenated regions can be up to three times greater than in a poorly vasculated portion of the tumour.


Besides  tumour hypoxia , the oxygen effect is also relevant to  hypoxia  conditions present in the normal physiology of  stem cell  niches such as the  endosteum  adjacent to bone in  bone marrow [ 1 ]  and the  epithelium layer  of the  intestine . [ 2 ]  In addition, there are non-malignant diseases where oxygenated tissues can become hypoxic such as in stenosed  coronary arteries  associated with  cardiovascular disease . [ 3 ]


Holthusen (1921) [ 4 ]  first quantified the oxygen effect finding 2.5 to 3.0-fold less hatching eggs of the  nematode   Ascaris  in oxygenated compared to anoxic conditions, which was incorrectly assigned to changes in  cell division . However, two years later, Petry (1923) [ 5 ]  first attributed oxygen tension as affecting  ionizing radiation  effects on vegetable seeds. Later, the implications of the effects of oxygen on  radiotherapy  were discussed by Mottram (1936). [ 6 ]


A key observation limiting hypotheses to explain the biological mechanisms of the oxygen effect is that the gas  nitric oxide  is a  radiosensitizer  with similar effects to oxygen observed in tumour cells. [ 7 ]  Another important observation is that oxygen must be present at irradiation or within milliseconds afterward for the oxygen effect to take place. [ 8 ]


The best known explanation of the oxygen effect is the oxygen fixation hypothesis developed by Alexander in 1962, [ 9 ]  which posited that radiation-induced non-restorable or "fixed" nuclear  DNA lesions  are lethal to cells in the presence of  diatomic oxygen . [ 10 ] [ 11 ]  Recent hypotheses include one based on oxygen-enhanced damage from first principles. [ 12 ]  Another hypothesis posits that ionizing radiation provokes  mitochondria  to produce reactive oxygen (and nitrogen species), which are leakage during  oxidative phosphorylation  that varies with a hyperbolic saturation relationship observed with both the oxygen and nitric oxide effects. [ 13 ]


The oxygen effect is quantified by measuring the radiation sensitivity or  Oxygen Enhancement Ratio  (OER) of a particular biological effect (e.g.,  cell death  or  DNA damage ), [ 14 ]  which is the ratio of doses under pure oxygen and anoxic conditions. Consequently, OER varies from unity in anoxia to a maximum value for 100% oxygen of typically up to three for low ionizing-density-radiation ( beta -,  gamma -, or  x-rays ), or so-called low  linear energy transfer  (LET) radiations.


Radiosensitivity varies most rapidly for oxygen partial pressures below ~1% atmospheric (Fig. 1). Howard-Flanders and Alper (1957) [ 15 ]  developed a formula for the  hyperbolic  function of OER and its variation with oxygen concentration, or oxygen pressure in air.


Radiobiologists  identified additional characteristics of the oxygen effect that influence radiotherapy practices. They found that the maximum OER value diminishes as the  ionizing -density of the radiation increases (Fig. 2), from low-LET to high-LET radiations. [ 16 ]  The OER is unity irrespective of the  oxygen tension  for alpha-particles of high-LET around 200 keV/μm. The OER is reduced for low doses as evaluated for cultured mammalian cells exposed to  x-rays  under aerobic (21% O2, 159 mmHg) and anoxic (nitrogen) conditions. [ 17 ]  Typical  fractionation  treatments are daily 2 Gy exposures, as below this dose the so-called 'shoulder' or repair region of the  cell survival curve  is encroached upon reducing the OER (Fig. 3).


In  optics , a  pencil  or  pencil of rays , also known as a  pencil beam  or  narrow beam , is a geometric construct ( pencil of half-lines ) used to describe a  beam  or portion of a beam of  electromagnetic radiation  or charged  particles , typically in the form of a  cone  or  cylinder .


Antennas which strongly bundle in  azimuth  and  elevation  are often described as "pencil-beam" antennas. For example, a  phased array antenna  can send out a beam that is extremely thin. Such antennas are used for tracking radar, and the process is known as  beamforming .


In  optics , the  focusing  action of a  lens  is often described in terms of pencils of  rays .  In addition to conical and cylindrical pencils, optics deals with  astigmatic  pencils as well. [ 1 ]


In  electron optics ,  scanning electron microscopes  use narrow pencil beams to achieve a deep  depth of field . [ 2 ]


Ionizing radiation  used in  radiation therapy , whether  photons  or  charged particles , such as  proton therapy  and  electron therapy  machines, is sometimes delivered through the use of pencil beam scanning. [ 3 ]


In  backscatter X-ray  imaging a pencil beam of x-ray radiation is used to scan over an object to create an intensity image of the Compton-scattered radiation.


A 1675 work describes a pencil as "a double cone of rays, joined together at the base." [ 4 ]  In his 1829  A System of Optics ,  Henry Coddington  defines a pencil as being "a parcel of light proceeding from some one point", whose form is "generally understood to be that of a right cone" and which "becomes cylindrical when the origin is very remote". [ 5 ]


This  optics -related article is a  stub . You can help Wikipedia by  expanding it .


Pencil beam scanning  is the practice of steering a beam of radiation or charged particles across an object. It is often used in  proton therapy , to reduce unnecessary radiation exposure to surrounding non-cancerous cells.


Ionizing radiation   photons  or  x-rays  ( IMRT ) use pencil beam scanning to precisely target a tumor. [ 1 ]  Photon pencil beam scans are defined as crossing of two beams to a fine point.


Several  charged particles  devices used with  Proton therapy  cancer centers use pencil beam scanning. [ 2 ]  The newer proton therapy machines use a pencil beam scanning technology. [ 3 ]
This technique is also called spot scanning. [ 4 ]  The  Paul Scherrer Institute  was the developer of spot beam. [ 5 ]


Varian's IMPT system uses all pencil-beam controlled protons where the beam intensity can also be controlled at this small level. This can be done by going back and forth over a previously radiated area during the same radiation session.


In  radiotherapy , a  percentage depth dose curve  (PDD) (sometimes  percent  depth dose curve) relates the  absorbed dose  deposited by a radiation beam into a medium as it varies with depth along the axis of the beam. The dose values are divided by the maximum dose, referred to as d max , yielding a plot in terms of percentage of the maximum dose. Dose measurements are generally made in water or "water equivalent" plastic with an  ionization chamber , since water is very similar to human tissue with regard to radiation scattering and absorption.


Percent depth dose (PDD), which reflects the overall percentage of dose deposited as compared to the depth of maximum dose, depends on the depth of interest, beam energy, field size, and SSD (source to surface distance) as follows. Of note, PDD generally refers to depths  greater than  the depth of maximum dose


Positron emission tomography for bone imaging,  as an  in vivo  tracer technique, allows the measurement of the regional concentration of  radioactivity  proportional to the image  pixel  values averaged over a region of interest (ROI) in bones. Positron emission tomography is a  functional imaging  technique that uses [ 18 F]NaF  radiotracer  to visualise and quantify regional  bone metabolism  and blood flow. [ 18 F]NaF has been used for imaging bones for the last 60 years. This article focuses on the  pharmacokinetics  of [ 18 F]NaF in bones, and various semi-quantitative and quantitative methods for quantifying regional bone metabolism using [ 18 F]NaF PET images.


The measurement of regional bone metabolism is critical to understand the  pathophysiology  of metabolic bone diseases.


The chemically stable  anion  of  Fluorine-18-Fluoride  is a  bone -seeking radiotracer in skeletal imaging. [ 18 F]NaF has an affinity to deposit at areas where the bone is newly mineralizing. [ 5 ] [ 7 ] [ 8 ] [ 9 ] [ 10 ]  Many studies have [ 18 F]NaF PET to measure  bone metabolism  at the  hip , [ 3 ]   lumbar spine , and  humerus . [ 11 ]  [ 18 F]NaF is taken-up in an exponential manner representing the equilibration of tracer with the extracellular and cellular fluid spaces with a  half-life  of 0.4 hours, and with kidneys with a half-life of 2.4 hours. [ 12 ]  The single passage extraction of [ 18 F]NaF in bone is 100%. [ 13 ]  After an hour, only 10% of the injected activity remains in the  blood . [ 14 ]


18 F- ions are considered to occupy  extracellular fluid  spaces because, firstly, they equilibrate with  transcellular fluid  spaces and secondly, they are not entirely extracellular ions. [ 15 ] [ 16 ] [ 17 ]  Fluoride undergoes equilibrium with  hydrogen fluoride , which has a high permeability allowing fluoride to cross the plasma blood  membrane . [ 18 ]  The fluoride circulation in  red blood cells  accounts for 30%. [ 19 ]  However, it is freely available to the bone surface for uptake because the equilibrium between erythrocytes and plasma is much faster than the capillary transit time. This is supported by studies reporting 100% single-passage extraction of whole-blood  18 F- ion by bone [ 13 ]  and the rapid release of  18 F- ions from erythrocytes with a rate constant of 0.3 per second. [ 20 ]


[ 18 F]NaF is also taken-up by immature erythrocytes in the  bone marrow , [ 21 ]  which plays a role in fluoride kinetics. [ 22 ]  The plasma protein binding of [ 18 F]NaF is negligible. [ 23 ]  [ 18 F]NaF renal clearance is affected by diet [ 24 ]  and  pH  level, [ 25 ]  due to its re-absorption in the nephron, which is mediated by hydrogen fluoride. [ 26 ]  However, large differences in  urine flow rate [ 19 ]  are avoided for controlled experiments by keeping patents well hydrated. [ 21 ]


The exchangeable pool and the size of the metabolically active surfaces in bones determines the amount of tracer accumulated or exchanged [ 27 ]  with bone  extracellular fluid , [ 28 ]   chemisorption  onto hydroxyapatite crystals to form fluorapatite, [ 14 ] [ 29 ] [ 9 ]  as shown in Equation-1: [ 30 ] [ 31 ]


C

 a

 10

 (
 P

 O

 4

 )

 6

 (
 O
 H

 )

 2

 +
 2
 F
 −
 =>
 C

 a

 10

 (
 P

 O

 4

 )

 6

 F

 2

 +
 2.
 O
 H
 −

 {\displaystyle Ca_{10}(PO_{4})_{6}(OH)_{2}+2F-=>Ca_{10}(PO_{4})_{6}F_{2}+2.OH-}

                                                                            Equation-1


Fluoride ions from the crystalline matrix of bone are released when the bone is remodelled, thus providing a measure of the rate of bone metabolism. [ 32 ] [ 33 ] [ 34 ]


The  standardized uptake value  (SUV) is defined as tissue concentration (KBq/ml) divided by activity injected normalized for  body weight . [ 35 ]


The SUV measured from the large ROI smooths out the noise and, therefore, more appropriate in [ 18 F]NaF bone studies as the radiotracer is fairly uniformly taken up throughout the bone. The measurement of SUV is easy, [ 36 ]  cheap, and quicker to perform, making it more attractive for clinical use. It has been used in diagnosing and assessing the efficacy of therapy. [ 37 ] [ 38 ]  SUV can be measured at a single site, or the whole skeleton using a series of static scans and restricted by the small field-of-view of the PET scanner. [ 32 ]