Monday, 19 January 2015

Health Care and Ionizing Radiation

Definitions:

Radiation: is “the transfer of energy as electromagnetic waves or as moving particles” (Oxford English Dictionary). Examples of non-ionizing radiation include light, radio waves, microwaves, heat, electromagnetic  waves of cell phones and Wi-Fi networks.

Ionizing Radiation: radiation that has enough energy to dislodge electrons from atoms and molecules to form ions and free radicals.

Isotopes are different kinds of atoms of the same element – just as German shepherds and collies are different breeds of the same thing, dogs. They will possess the same number of protons but differ in the number of neutrons in the nucleus.

Radioisotopes are isotopes that emit radioactivity as gamma rays, beta particles or alpha particles.

Radioactive Decay:  the process whereby a radioisotope gives off energy and/or particles and becomes a different element  If the new element is also radioactive, it, too, will change into a third element. A series of these changes is called a decay chain. A commonly used radioisotope, technetium-99m, has a two step decay chain from Tc-99m to Tc-99 and then to stable ruthenium-99.  Uranium-238 (“depleted uranium” – called so only because it has no value in nuclear power plants or nuclear weapons, unlike its fissionable isotope, uranium-235) undergoes a 14 step decay chain before reaching stable lead-206.

Half-life: The length of time taken for one half of the radioactivity in a sample of an element to dissipate.  In effect, this could mean that half of the sample has become another element. For example, the half-life of caesium-131, used in radiopharmaceuticals, is 10 days so after ten days one half of the caesium has become xenon-131. Ten half-lives, 100 days, results in only 1/1024 of the original caesium-131.

Radiopharmaceuticals: this term covers a range of drugs, chemicals or elements that are chemically bound to radioisotopes.  When used for a medical examination, a radiopharmaceutical may be referred to as a tracer. As the ultimate “designer drugs”, they are designed to be absorbed by specific cells or organs in the body and may be introduced by injection, inhalation, or ingestion. The optimum radioisotope is short-lived, delivers high energy to a specific target and decays to a stable product. For example: Used for treatment of hyperthyroidism or thyroid cancer, iodine-131 delivers high energy beta radiation to the thyroid and decays with a half-life of eight days to stable xenon-131.

X-rays are short high-energy waves that are released in the form of excess energy when an electrically produced electron collides with, or has its path altered by a tungsten target. The process of production is highly controlled. Modern machines are very focussed with little scatter.

Gamma rays are very similar to x-rays in that they are also short high-energy waves but they are given off by radioisotopes during the process of radioactive decay. Radiopharmaceuticals make use of gamma radiation because they will concentrate in organs or blood which can be picked up on photographic film.

Beta particles are electrons emitted from the nucleus of an atom during decay – as a neutron changes to a proton, it emits an electron. They have poor penetrating energy but are more dangerous when inhaled or ingested. Tritium, the radioactive form of hydrogen found naturally in extremely small amounts but a common gaseous release from nuclear power plants, decays by beta emission.

Alpha particles are equivalent to the nucleus of a helium atom – two protons and two neutron. They are slow-moving and easily stopped by skin. They are considered 20x more biologically damaging than either gamma rays or beta particles when taken internally. Uranium-238 and radium-226 decay by alpha particle emission to thorium-234 and radon-222 respectively.

Electron capture: an electron from an atom’s circulating electrons is pulled into the nucleus. Gamma rays are released as a proton in the nucleus becomes a neutron; the atom becomes the next lower element in the periodic table.  Palladium-103 is one such radioisotope sometimes used for prostate cancer. Its decay product is stable rhodium-103.

Radiotherapy: the use of ionizing radiation for treatment usually of tumours.

History:

In 1895, x-rays were discovered by Wilhelm Roentgen, a professor of physics in Bavaria, when he was experimenting with electrons. He made the first x-ray immortalizing his wife’s hand and her wedding ring. Physicians were quick to jump on the bandwagon of a technology that would differentiate bones from soft tissue. The first x-ray department was opened in 1896 in Glascow, Scotland. Side effects were not far behind when, in the same year, an Austrian doctor reported that he had severely burned a patient’s back.  

Although by 1905, reddened skin was a known side-effect of x-rays, it was believed that cancer was merely a progression of the radiation dermatitis. The first regulations governing exposure were established as “tolerance levels” – if reddening of the skin didn’t occur, exposure was below the tolerance level.  While physicians experimented with their new tool, its unregulated use left such damage in its wake that, in 1936, a monument was built in Hamburg, Germany, to mark the end of this era and to commemorate the thousands of people and hundreds of medical staff who had perished as a result of x-ray exposure.

Radiotherapy was used as early as 1896 when a medical student in Chicago reported using x-rays to reduce the size of a cancerous nodule of the breast. Fifteen years of trial and error – many seriously injured patients and use of radiotherapy for everything from hair removal to plantar’s warts and cancerous tumours – passed before an Austrian physician suggested that using fractionated doses over several days would result in less tissue damage. By 1922, this was common practice. In 1930, its use for hair removal was forbidden. Exposing tumours to radium-226 or badly focussed x-rays was supplanted by cobalt-60 when its production in cyclotrons made it widely available in the 1950’s. Even so, while the patients were often cured, the side effects were lifelong scarring and erosive dermatitis.

Effects of ionizing radiation on a cell:[i]


This diagrams a simple triage of possible outcomes when ionizing radiation passes through a biological cell: no effect, death or mutation, the latter having two outcomes - if the cellular function is otherwise controlled by the body, there may be no effect but if the cell is altered enough, it may spawn a chronic disease, affect the reproduction of the cells to produce a cancer or affect the germ cells for the next generation so that there is a inherited defect.

Medical uses of radioactivity:

1)     External:
a)     X-rays – machine generated ionizing radiation.
b)     CT (CAT) scans – Computerized (or “computed”) axial tomography is a series of x-rays taken at different levels through a body part like slices of bread and computer-manipulated to form a three dimensional image.
c)     External radiotherapy – radiotherapy is generated by linear accelerators that focus high-energy x-rays at tumours preferentially destroying cancer cells. Older units targeted tumours with gamma rays from cobalt-60 but were limited by the energy that could be generated. They continue to be used in low-resource settings.

2)     Internal:
a)     Scanning materials and devices:
i)      Gallium scans – The earliest and most widely applied radiopharmaceutical was a gallium-67 salt (citrate or nitrate) making use of a short half-life of 3.26 days and ease of production in  a cyclotron. As it decays to zinc-67, it emits gamma rays which were picked up by photographic film before the advent of gamma cameras and computers. Gallium behaves like ferric iron and concentrates in areas of inflammation. It has mostly been supplanted by other tracers but the fact that it can be absorbed by both dead and alive white blood cells gives it special value in identifying places where they accumulate such as lymphomas, osteomyelitis and abscesses.
ii)     PET scans – Positron emission tomography scans show how the body works. A simple gamma camera detects gamma rays and a computer generates a three-dimensional image in contrasted colours. The most commonly used radioisotope is fluorine-18 with a half-life of 1.83 hours produced in cyclotrons close to the hospitals. It decays to stable oxygen-18.  The ease with which fluorine can be bound to sugar molecules makes it useful to examine places where rapid metabolism occurs.
iii)   SPECT scans – Single photon emission computed tomography scans use moving gamma cameras in order to provide the three-dimensional image. The image is less specific but cheaper to produce. For intracranial examination, technetium-99m is attached to exametazime, a molecule that crosses the blood-brain barrier.
iv)    MIBI scans using the radioisotope technetium-99m have special use in parathyroid and heart scans. MIBI is short for methoxyisobutylisonitrile which is picked up by actively metabolizing mitochondria. Two scans are usually performed, an early scan and one after a “wash-out” period.
v)     MUGA scans: Multi-gated acquisition scans also involve the use of technetium-99m in this case attached to a pertechnetate ion which binds to red blood cells. Typically sixteen images are taken using the contractions of the heart to trigger (gate) the pictures.

b)     Brachytherapy – (from Greek “brachys” meaning “short distance”) the radioactive source is implanted directly into or close to the tumour itself. Ideal elements for brachytherapy deliver a high dose in a short period of time minimizing the effect upon healthy cells. The first implantable radiotherapeutic materials were alpha particle emitters like radium-226.    
i)      Permanent brachytherapy: small “seeds” of the radioactive element are placed into the tumour - Iridium-192 which decays by strong gamma and beta emission is commonly used for prostate cancer but other elements, caesium-131, iodine-125 and palladium-46 have also been used.
ii)     Temporary brachytherapy: The radiopharmaceutical is delivered by catheter, needle or applicator inserted into the body cavity or interstitially. Doseages may be high, low or delivered intermittently. Iridium-192 (which decays by electron capture to platinum-192) is a radioisotope frequently used.

Putting Ionizing Radiation Exposure in Perspective[ii]:

Source of Radiation:                                      Radiation dose in mSv:             

Airport passenger scan                                  0.0001
Hand or foot x-ray (one view)                         0.005
Watching tv (4 hrs/day)                                   0.01/yr
Bitewing dental x-ray                                      0.03
Air travel: Toronto-Vancouver return               0.05
Chest x-ray (one view)                                    0.10
Nuclear medicine thyroid scan                        0.14
Dental panoramic                                            0.15
Pelvic x-ray                                                      0.7
Screening mammogram (four views)               0.7
Thoracic spine x-ray                                        1.0
Lumbar spine x-ray                                          1.5
Nuclear medicine lung scan                             2.0
Background radiation (average Cndn)             2.5
Nuclear medicine bone scan                            4.2
Nuclear cardiac diagnostic test (MIBI)            10
Abdominal CT scan                                         10
Smoking (20 cigs/day)                                     53

Hazards: 

When the ionizing radiation of x-rays or gamma rays pass through a body, no radioactivity remains in the body. A trail of damaged structural proteins, enzymes and nucleic acids marks their passage. The damage done is cumulative, the probability of genetic defects, cancers, and life-shortening effects increases over a person’s lifetime. By and large, the greatest body burden of ionizing radiation for North Americans is the result of medical diagnostic or therapeutic uses.

The medical profession is so enamoured with diagnostic and treatment using ionizing radiation that even though two researchers, Dr. Alice Stewart in the UK in the 1950’s and Dr. Rosalie Bertell in the USA in the 1960’s, established the link between a single chest x-ray on a woman in pregnancy and an increased risk of leukemia in the offspring, it was not until the 1970’s that patient shielding became standard practice and performing x-rays during pregnancy severely limited. An entirely new phase of medical excitement over technology occurred over CT scans[iv]. Given that these scans deliver in order of magnitude at least 75 times the radiation of a chest x-ray, it should be no surprise that the incidence of cancer increases with the number of CT scans.[v]

Radiotherapy using radioisotopes also has its risks.  Although the intention is to avoid irradiation of healthy cells, some will inevitably be exposed to radiation. The possibility exists that one of these cells will mutate and lead to a secondary cancer. One study estimated that 8% of secondary cancers are caused by radiotherapy.[vi] This is very difficult to calculate because the same risks present for the first cancer may still exist (for example, smoking). The risk will also vary with amounts of radiation exposure, parts of the body exposed and the age of the patient. In 2011, researchers at McGill reviewed more than eighty thousand patient charts and concluded that the risk of cancer from low-dose imaging techniques increased 3% for every 10 mSv of radiation received.[vii]

Finally, concern exists over the variety of decay products from radioisotopes used in radiopharmaceuticals. Although the tracers may decay rapidly to a stable element, their progeny may not. While fluorine-18 decays to oxygen-18 which is stable, technetium-99m decays to technetium-99 which is also radioactive with a half-life of 211,000 years.

In conclusion, ionizing radiation has literally opened the living human body to knifeless dissection but carries its own risks. It is challenging to “first do no harm”[viii] and curb our ever-increasing desire to know more about our patient’s body or disease – whether or not we can treat it.




[i] Adapted by F. Oelck from Grenier, Gilles W. (2006). Lignes Directrices Pour Le Depistage De La Contamination Et La Decontamination Des Personnes Lors D’une Urgence Nucleaire. As posted online at: www.urgencenucleaire.qc.ca/documentation/decontamination_perspdf, [May 10th, 2011].
[ii] Modified based on Society of Nuclear Medicine, “Beneficial Medical Uses of Radiation,” www.molecularimagingcentre.org/index.cfm?PageID=7083>; American Dental Association, “Oral Health Topics,” www.ada.org/2760.aspx., Neil Savage, “X-ray Body Scanners Arriving at Airports,” spectrum.ieee.org/biomedical/imaging/xray-body-scanners-arriving-at-airports.
[iii] For example, varies with elevation, surroundings (mountains of granite or flat prairies), wind and other geographic factors – such as mines, nuclear power emissions, basements (radon). 
[iv] James C. Worrall, Sadia Jama, Ian G. Stiell, “Radiation doses to emergency department patients undergoing computed tomography” Canadian Journal of Emergency Medicine, 2104;16(6):477-484 cjem-online.ca/v16/n06/p477
[v] Carina Storrs, “How Much Do CT Scans Increase the Risk of Cancer? Scientific American, 309, Issue 1, Jun 18, 2013 scientificamerican.com/article/how-much-ct-scans-increase-risk-cancer/
[vi] “Benefits of Radiotherapy Outweigh Small Increased Risk of Second cancer,” Ecancernews, 2011 ecancermedicalscience.com/news-insider-news.asp?itemid=1660
[vii] Mark J. Eisenberg, Johathan Afilalo, Patrick R. Lawler, Michal Abramhamowicz, Hugues Richard, and Louise Pilote, “Cancer Risk Related to Low-Dose Ionizing radiation from cardiac Imaging in Patients after Acute Myocardial Infarction,” Canadian Medical Association Journal 183 (March 8, 2011): 430-436.
[viii] Erroneously thought to be from the Hippocratic oath but attributed to Dr. Thomas Inman according to Wikipedia, en.wikipedia.org/wiki/Thomas_Inman

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