Nuclear medicine
Nuclear medicine is a branch or specialty of medicine and medical imaging that uses radioactive isotopes (radionuclides) and relies on the process of radioactive decay in the diagnosis and treatment of disease.
In nuclear medicine procedures, radionuclides are combined with other chemical compounds or pharmaceuticals to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs or cellular receptors. This property of radiopharmaceuticals allows nuclear medicine the ability to image the extent of a disease-process in the body, based on the cellular function and physiology, rather than relying on physical changes in the tissue anatomy. In some diseases nuclear medicine studies can identify medical problems at an earlier stage than other diagnostic tests.
Treatment of disease, based on metabolism or uptake or binding of a ligand, may also be accomplished, similar to other areas of pharmacology. However, radiopharmaceuticals rely on the tissue-destructive power of short-range ionizing radiation.
Description of the field
In nuclear medicine imaging, radiopharmaceuticals are taken internally, for example intravenously or orally. Then, external detectors (gamma cameras) capture and form images from the radiation emitted by the radiopharmaceuticals. This process is unlike a diagnostic X-ray where external radiation is passed through the body to form an image.
There are several techniques of diagnostic nuclear medicine. Scintigraphy ("scint") is the use of internal radioisotopes to create two-dimensional[1] images. SPECT is a 3D tomographic technique that uses gamma camera data from many projections and can be reconstructed in different planes. Positron emission tomography (PET) uses coincidence detection to image functional processes.
Nuclear medicine tests differ from most other imaging modalities in that diagnostic tests primarily show the physiological function of the system being investigated as opposed to traditional anatomical imaging such as CT or MRI. Nuclear medicine imaging studies are generally more organ or tissue specific (e.g.: lungs scan, heart scan, bone scan, brain scan, etc.) than those in conventional radiology imaging, which focus on a particular section of the body (e.g.: chest X-ray, abdomen/pelvis CT scan, head CT scan, etc.). In addition, there are nuclear medicine studies that allow imaging of the whole body based on certain cellular receptors or functions. Examples are whole body PET scan or PET/CT scans, gallium scans, indium white blood cell scans, MIBG and octreotide scans.
While the ability of nuclear metabolism to image disease processes from differences in metabolism is unsurpassed, it is not unique. Certain techniques such as fMRI image tissues (particularly cerebral tissues) by blood flow, and thus show metabolism. Also, contrast-enhancement techniques in both CT and MRI show regions of tissue which are handling pharmaceuticals differently, due to an inflammatory process.
Diagnostic tests in nuclear medicine exploit the way that the body handles substances differently when there is disease or pathology present. The radionuclide introduced into the body is often chemically bound to a complex that acts characteristically within the body; this is commonly known as a tracer. In the presence of disease, a tracer will often be distributed around the body and/or processed differently. For example, the ligand methylene-diphosphonate (MDP) can be preferentially taken up by bone. By chemically attaching technetium-99m to MDP, radioactivity can be transported and attached to bone via the hydroxyapatite for imaging. Any increased physiological function, such as due to a fracture in the bone, will usually mean increased concentration of the tracer. This often results in the appearance of a 'hot-spot' which is a focal increase in radio-accumulation, or a general increase in radio-accumulation throughout the physiological system. Some disease processes result in the exclusion of a tracer, resulting in the appearance of a 'cold-spot'. Many tracer complexes have been developed to image or treat many different organs, glands, and physiological processes.
Hybrid scanning techniques
In some centers, the nuclear medicine scans can be superimposed, using software or hybrid cameras, on images from modalities such as CT or MRI to highlight the part of the body in which the radiopharmaceutical is concentrated. This practice is often referred to as image fusion or co-registration, for example SPECT/CT and PET/CT. The fusion imaging technique in nuclear medicine provides information about the anatomy and function, which would otherwise be unavailable, or would require a more invasive procedure or surgery.
Practical concerns in nuclear imaging
The amount of radiation from diagnostic nuclear medicine procedures is kept within a safe limit and follows the "ALARA" (As Low As Reasonably Achievable) principle. The radiation dose from nuclear medicine imaging varies greatly depending on the type of study. The effective radiation dose can be lower than or compatible to the annual background radiation dose. It can also be in the range or higher than the radiation dose from an abdomen/pelvis CT scan.[2]
Some nuclear medicine procedures require special patient preparation, before the study, to obtain the most accurate result. Pre-imaging preparations may include dietary preparation or withholding of certain medications. Patients are encouraged to consult with the nuclear medicine department prior to a scan.
Nuclear medicine therapy
In nuclear medicine therapy, the radiation treatment dose is also administered internally (e.g. intravenous or oral routes) rather from an external radiation source.
The radiopharmaceuticals used in Nuclear Medicine therapy emit ionizing radiation that travels only a short distance, thereby minimizing unwanted side effects and damage to noninvolved organs or nearby structures. Most Nuclear Medicine therapies can be performed as outpatient procedures since there are few side effects from the treatment and the radiation exposure to the general public can be kept within a safe limit. Common Nuclear Medicine therapies include 131I-sodium iodide for hyperthyroidism and thyroid cancer, Yttrium-90-ibritumomab tiuxetan (Zevalin) and Iodine-131-tositumomab (Bexxar) for refractory Lymphoma, 131I-MIBG (metaiodobenzylguanidine) for neuroendocrine tumors, and palliative bone pain treatment with Samarium-153 or Strontium-89. In some centers the nuclear medicine department may also use implanted capsules of isotopes (brachytherapy) to treat cancer.
Most nuclear medicine therapies will also require appropriate patient preparation prior to a treatment. Therefore, consultation with the Nuclear Medicine department is recommended prior to therapy.
Molecular medicine
In the future, nuclear medicine may be known as molecular medicine. As our understanding of biological processes in the cells of living organism expands, specific probes can be developed to allow visualization, characterization, and quantification of biologic processes at the cellular and subcellular levels.[2] Nuclear Medicine is an ideal specialty to adapt to the new discipline of molecular medicine, because of its emphasis on function and its utilization of imaging agents that are specific for a particular disease process.
History
The history of nuclear medicine is rich with contributions from gifted scientists across different disciplines in physics, chemistry, engineering, and medicine. The multidisciplinary nature of Nuclear Medicine makes it difficult for medical historians to determine the birthdate of Nuclear Medicine. This can probably be best placed between the discovery of artificial radioactivity in 1934 and the production of radionuclides by Oak Ridge National Laboratory for medicine related use, in 1946.[3]
Many historians consider the discovery of artificially produced radioisotopes by Frederic Joliot-Curie and Irene Joliot-Curie in 1934 as the most significant milestone in Nuclear Medicine.[3] In February 1934, they reported the first artificial production of radioactive material in the Nature journal, after discovering radioactivity in aluminum foil that was irradiated with a polonium preparation. Their work built upon earlier discoveries by Wilhelm Konrad Roentgen for X-ray, Henri Becquerel for radioactive uranium salts, and Marie Curie (mother of Irene Curie) for radioactive thorium, polonium and coining the term "radioactivity." Taro Takemi studied the application of nuclear physics to medicine in the 1930s. The history of Nuclear Medicine will not be complete without mentioning these early pioneers.
Nuclear medicine gained public recognition as a potential specialty on December 7, 1946 when an article was published in the Journal of the American Medical Association by Sam Seidlin. The article described a successful treatment of a patient with thyroid cancer metastases using radioiodine (I-131). This is considered by many historians as the most important article ever published in Nuclear Medicine.[4] Although, the earliest use of I-131 was devoted to therapy of thyroid cancer, its use was later expanded to include imaging of the thyroid gland, quantification of the thyroid function, and therapy for hyperthyroidism.
Widespread clinical use of Nuclear Medicine began in the early 1950s, as knowledge expanded about radionuclides, detection of radioactivity, and using certain radionuclides to trace biochemical processes. Pioneering works by Benedict Cassen in developing the first rectilinear scanner and Hal O. Anger's scintillation camera (Anger camera) broadened the young discipline of Nuclear Medicine into a full-fledged medical imaging specialty.
In these years of Nuclear Medicine, the growth was phenomenal. The Society of Nuclear Medicine was formed in 1954 in Spokane, Washington, USA. In 1960, the Society began publication of the Journal of Nuclear Medicine, the premier scientific journal for the discipline in America. There was a flurry of research and development of new radionuclides and radiopharmaceuticals for use with the imaging devices and for in-vitro studies5.
Among many radionuclides that were discovered for medical-use, none were as important as the discovery and development of Technetium-99m. It was first discovered in 1937 by C. Perrier and E. Segre as an artificial element to fill space number 43 in the Periodic Table. The development of generator system to produce Technetium-99m in the 1960s became a practical method for medical use. Today, Technetium-99m is the most utilized element in Nuclear Medicine and is employed in a wide variety of Nuclear Medicine imaging studies.
By the 1970s most organs of the body could be visualized using Nuclear Medicine procedures. In 1971, American Medical Association officially recognized nuclear medicine as a medical specialty.[5] In 1972, the American Board of Nuclear Medicine was established, cementing Nuclear Medicine as a medical specialty.
In the 1980s, radiopharmaceuticals were designed for use in diagnosis of heart disease. The development of single photon emission tomography, around the same time, led to three-dimensional reconstruction of the heart and establishment of the field of Nuclear Cardiology.
More recent developments in Nuclear Medicine include the invention of the first positron emission tomography scanner (PET). The concept of emission and transmission tomography, later developed into single photon emission computed tomography (SPECT), was introduced by David E. Kuhl and Roy Edwards in the late 1950s [citation needed]. Their work led to the design and construction of several tomographic instruments at the University of Pennsylvania. Tomographic imaging techniques were further developed at the Washington University School of Medicine. These innovations led to fusion imaging with SPECT and CT by Bruce Hasegawa from University of California San Francisco (UCSF), and the first PET/CT prototype by D. W. Townsend from University of Pittsburgh in 1998 [citation needed].
PET and PET/CT imaging experienced slower growth in its early years owing to the cost of the modality and the requirement for an on-site or nearby cyclotron. However, an administrative decision to approve medical reimbursement of limited PET and PET/CT applications in oncology has led to phenomenal growth and widespread acceptance over the last few years. PET/CT imaging is now an integral part of oncology for diagnosis, staging and treatment monitoring.
Source of radioisotopes
About two thirds of the world's supply of medical isotopes are produced at the Chalk River Laboratories in Chalk River, Ontario, Canada. The Canadian Nuclear Safety Commission ordered the NRU reactor to be shut down on November 18, 2007 for regularly scheduled maintenance and an upgrade of the safety systems to modern standards. The upgrade took longer than expected and in December 2007 a critical shortage of medical isotopes occurred. The Canadian government unanimously passed emergency legislation, allowing the reactor to re-start on 16 December 2007, and production of medical isotopes to continue.
The Chalk River reactor is used to irradiate materials with neutrons which are produced in great quantity during the fission of U-235. These neutrons change the nucleus of the irradiated material by adding a neutron, or by splitting it in the process of nuclear fission. In a reactor, one of the fission products of uranium is molybdenum-99 which is extracted and shipped to radiopharmaceutical houses all over North America. The Mo-99 radioactively beta decays with a half-life of 2.7 days, turning initially into Tc-99m, which is then extracted (milked) from a "moly cow" (see technetium-99m generator). The Tc-99m then further decays, while inside a patient, releasing a gamma photon which is detected by the gamma camera. It decays to its ground state of Tc-99, which is relatively non-radioactive compared to Tc-99m.
The most commonly used radioisotope in PET F-18, is not produced in any nuclear reactor, but rather in a circular acclererator called a cyclotron. The cyclotron is used to accelerate protons to bombard the stable heavy isotope of oxygen O-18. The O-18 constitutes about 0.20% of ordinary oxygen (mostly O-16), from which it is extracted. The F-18 is then typically used to make FDG (see this link for more information on this process).
| isotope | symbol | Z | T1/2 | decay | photons | β |
|---|---|---|---|---|---|---|
| Imaging: | ||||||
| fluorine-18 | 18F | 9 | 109.77 m | β+ | 511 (193%) | 0.664 (97%) |
| gallium-67 | 67Ga | 31 | 3.26 d | ec | 93 (39%), 185 (21%), 300 (17%) |
- |
| krypton-81m | 81mKr | 36 | 13.1 s | IT | 190 (68%) | - |
| rubidium-82 | 82Rb | 37 | 1.27 m | β+ | 511 (191%) | 3.379 (95%) |
| technetium-99m | 99mTc | 43 | 6.01 h | IT | 140 (89%) | - |
| indium-111 | 111In | 49 | 2.80 d | ec | 171 (90%), 245 (94%) |
- |
| iodine-123 | 123I | 53 | 13.3 h | ec | 159 (83%) | - |
| xenon-133 | 133Xe | 54 | 5.24 d | β- | 81 (31%) | 0.364 (99%) |
| thallium-201 | 201Tl | 81 | 3.04 d | ec | 69–83* (94%), 167 (10%) |
- |
| Therapy: | ||||||
| yttrium-90 | 90Y | 39 | 2.67 d | β- | - | 2.280 (100%) |
| iodine-131 | 131I | 53 | 8.02 d | β- | 364 (81%) | 0.807 (100%) |
|
Z = atomic number, the number of protons; T1/2 = half-life; decay = mode of decay | ||||||
A typical nuclear medicine study involves administration of a radionuclide into the body by intravenous injection in liquid or aggregate form, ingestion while combined with food, inhalation as a gas or aerosol, or rarely, injection of a radionuclide that has undergone micro-encapsulation. Some studies require the labeling of a patient's own blood cells with a radionuclide (leukocyte scintigraphy and red blood cell scintigraphy). Most diagnostic radionuclides emit gamma rays, while the cell-damaging properties of beta particles are used in therapeutic applications. Refined radionuclides for use in nuclear medicine are derived from fission or fusion processes in nuclear reactors, which produce radioisotopes with longer half-lives, or cyclotrons, which produce radioisotopes with shorter half-lives, or take advantage of natural decay processes in dedicated generators, i.e. molybdenum/technetium or strontium/rubidium.
The most commonly used intravenous radionuclides are:
- Technetium-99m (technetium-99m)
- Iodine-123 and 131
- Thallium-201
- Gallium-67
- Fluorine-18 Fluorodeoxyglucose
- Indium-111 Labeled Leukocytes
The most commonly used gaseous/aerosol radionuclides are:
Analysis
The end result of the nuclear medicine imaging process is a "dataset" comprising one or more images. In multi-image datasets the array of images may represent a time sequence (i.e. cine or movie) often called a "dynamic" dataset, a cardiac gated time sequence, or a spatial sequence where the gamma-camera is moved relative to the patient. SPECT (single photon emission computed tomography) is the process by which images acquired from a rotating gamma-camera are reconstructed to produce an image of a "slice" through the patient at a particular position. A collection of parallel slices form a slice-stack, a three-dimensional representation of the distribution of radionuclide in the patient.
The nuclear medicine computer may require millions of lines of source code to provide quantitative analysis packages for each of the specific imaging techniques available in nuclear medicine.
Time sequences can be further analysed using kinetic models such as multi-compartment models or a Patlak plot.
Radiation dose
A patient undergoing a nuclear medicine procedure will receive a radiation dose. Under present international guidelines it is assumed that any radiation dose, however small, presents a risk. The radiation doses delivered to a patient in a nuclear medicine investigation present a very small risk of inducing cancer. In this respect it is similar to the risk from X-ray investigations except that the dose is delivered internally rather than from an external source such as an X-ray machine.
The radiation dose from a nuclear medicine investigation is expressed as an effective dose with units of sieverts (usually given in millisieverts, mSv). The effective dose resulting from an investigation is influenced by the amount of radioactivity administered in megabecquerels (MBq), the physical properties of the radiopharmaceutical used, its distribution in the body and its rate of clearance from the body.
Effective doses can range from 6 μSv (0.006 mSv) for a 3 MBq chromium-51 EDTA measurement of glomerular filtration rate to 37 mSv for a 150 MBq thallium-201 non-specific tumour imaging procedure. The common bone scan with 600 MBq of technetium-99m-MDP has an effective dose of 3 mSv (1).
Formerly, units of measurement were the curie (Ci), being 3.7E10 Bq, and also 1.0 grams of Radium (Ra-226); the rad (radiation absorbed dose), now replaced by the gray; and the rem (Röntgen equivalent man), now replaced with the sievert. The rad and rem are essentially equivalent for almost all nuclear medicine procedures, and only alpha radiation will produce a higher Rem or Sv value, due to its much higher Relative Biological Effectiveness (RBE). Alpha emitters are nowadays rarely used in nuclear medicine, but were used extensively before the advent of nuclear reactor and accelerator produced radioisotopes. The concepts involved in radiation exposure to humans is covered by the field of Health Physics.
Nuclear Medicine Careers
Nuclear medicine technologist
The information below is adapted from the Society of Nuclear Medicine (SNM) website on Technologist career. For more information and educational requirements, please see training [8]
The nuclear medicine technologist works closely with the nuclear medicine physician. Some of the technologist primary responsibilities are to:
- Prepare and administer radioactive chemical compounds, known as radiopharmaceuticals
- Perform patient imaging procedures using sophisticated radiation-detecting instrumentation
- Accomplish computer processing and image enhancement
- Analyze biologic specimens in the laboratory
- Provide images, data analysis, and patient information to the physician for diagnostic interpretation.
During an imaging procedure, the technologist works directly with the patient. The technologist:
- Gains the patient's confidence by obtaining pertinent history, describing the procedure and answering any questions
- Monitors the patient's physical condition during the course of the procedure
- Notes any specific patient's comments which might indicate the need for additional images or might be useful to the physician in interpreting the results of the procedure.
Nuclear medicine technologists work in a wide variety of clinical settings, such as
- Community hospitals
- University-affiliated teaching hospitals and medical centers
- Outpatient imaging facilities
- Public health institutions
- Government and private research institutes.
The physician career in nuclear medicine
Nuclear medicine physicians are primarily responsible for interpretation of diagnostic nuclear medicine scans and treatment of certain diseases, such as cancer, thyroid disease and palliative bone pain.
There are a variety of reasons why physicians have chosen to specialize in nuclear medicine. Some became nuclear medicine physicians because of their interest in nuclear physics and medical imaging. Others may have switched to nuclear medicine after training in other specialties, because of the regular work hours (on average about 8 to 10 hours a day). Others have chosen nuclear medicine because of research opportunities in molecular medicine or molecular imaging.
Nuclear medicine physicians frequently interact with other specialties in medicine and consult on a variety of clinical cases. A nuclear medicine report may save a patient from more invasive or high risk procedures, and/or lead to early disease diagnosis. Nuclear Medicine physicians can be called upon to consult on complex or equivocal clinical cases. Aside from consultations with other physicians, nuclear physicians may directly interact with patients through various nuclear medicine therapies (e.g.: I131 thyroid therapy, refractory lymphoma treatment, palliative bone pain therapy).
A disadvantage of a nuclear medicine career for a physician is that it suffers from low job turnover and a small job market, owing to the specialized nature of the field. Advantages of the field include job satisfaction and more regular hours than many fields of medicine, since very rarely are the procedures in this field performed on an emergency basis.
Nuclear medicine residency/training (physicians)
The information below is adapted from the American Board of Nuclear Medicine (ABNM). For more information, please see ABNM [9]
General professional education requirement in the United States of America: graduation from a medical school approved by the Liaison Committee on Medical Education or the American Association of Colleges of Osteopathic Medicine.
In USA the post-doctoral training in nuclear medicine can be approached from three different pathways:
- If the person has successfully completed an accredited radiology residency then additional ONE year of training in Nuclear Medicine is required to be eligible for ABNM board certification.
- If the person has successfully completed a clinical residency (e.g. Internal Medicine, Family Medicine, Surgery, Neurology, etc.) then an additional TWO years of training in Nuclear Medicine is required to be eligible for ABNM board certification.
- If the person has successfully completed one year of preparatory post-doctoral training (internship) then an additional THREE years of training in Nuclear Medicine is required to be eligible for ABNM board certification.
See also
Notes
- ^ thefreedictionary.com > scintigraphy Citing: Dorland's Medical Dictionary for Health Consumers, 2007 by Saunders; Saunders Comprehensive Veterinary Dictionary, 3 ed. 2007; McGraw-Hill Concise Dictionary of Modern Medicine, 2002 by The McGraw-Hill Companies
- ^ [www.molecularimagingcenter.org], Gambhir S. Just what is molecular medicine.
- ^ a b Edwards Cl: Tumor localizing radionuclides in retrospect and prospect. Semin Nucl Med 3:186–189, 1979.
- ^ Henkin R. et al: Nuclear Medicine. First edition 1996. ISBN 9780801677014.
- ^ http://interactive.snm.org/docs/whatisnucmed.pdf from the Society of Nuclear Medicine.
- ^ Eckerman KF, Endo A: MIRD: Radionuclide Data and Decay Schemes. Society for Nuclear Medicine, 2008. ISBN 978-0932004802
- ^ WWW Table of Radioactive Isotopes
- ^ Training
- ^ Acgme
Further reading
- Mas JC: A Patient's Guide to Nuclear Medicine Procedures: English-Spanish. Society of Nuclear Medicine, 2008. ISBN 978-0972647892
- Taylor A, Schuster DM, Naomi Alazraki N: A Clinicians' Guide to Nuclear Medicine, 2nd edition. Society of Nuclear Medicine, 2000. ISBN 978-0932004727
- Mark J. Shumate MJ, Kooby DA, Alazraki NP: A Clinician's Guide to Nuclear Oncology: Practical Molecular Imaging and Radionuclide Therapies. Society of Nuclear Medicine, January 2007. ISBN 978-0972647885
- Ell P, Gambhir S: Nuclear Medicine in Clinical Diagnosis and Treatment. Churchill Livingstone, 2004. (1950 pages) ISBN 978-0443073120
External links
- Society of Nuclear Medicine
- Brochure: What is Nuclear Medicine?
- Resource center: information about nuclear medicine
- International Atomic Energy Agency (IAEA), Division of Human Health, Nuclear Medicine
- RADAR Medical Procedure Radiation Dose Calculator and Consent Language Generator
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