Nuclear medicine uses radioactive tracer medications, called radiopharmaceuticals, along with medical imaging techniques, to produce images that show how an organ in the human body is functioning. Nuclear medicine can be used for research, diagnosis, or treatment of disease (The American Board of Nuclear Medicine). A specialist in nuclear medicine is called a nuclear medicine physician.
It is important to distinguish between general radiology and nuclear medicine. Radiology also uses medical imaging techniques to image the body, but these images show the anatomic structure (as opposed to the functioning) of organs in the body to help diagnose and treat illness and injury. Some examples of imaging techniques used by general radiologists (specialists in this field) include x-ray, MRI, or CT scan (UCSF Department of Radiology and Biomedical Imaging).
Nuclear medicine was officially recognized as its own medical specialty in 1971 with the subsequent establishment of the American Board of Nuclear Medicine (ABNM). The ABNM establishes requirements for acquiring and maintaining board certification in nuclear medicine in the United States. To be designated as board certified, a physician must complete a one-year internship and three years of nuclear medicine training after finishing medical school. If the physician is already a board certified radiologist, they must complete an additional 16 months of training in nuclear medicine. They must then pass an exam. Maintaining the board certification requires completion of continuing medical education hours yearly (The American Board of Nuclear Medicine).
History of Nuclear Medicine
Henri Becquerel (1852-1908)
The history of nuclear medicine starts with the serendipitous discovery of radioactivity in 1896 by Henri Becquerel, a French physicist. Becquerel noticed that uranium emitted a radiation that could be seen on a photographic plate. Thinking this was explained by the then newly discovered x-rays, he ran further experiments and discovered that the new rays differed in their electric and magnetic properties from x-rays. For this discovery, he shared the 1903 Nobel Prize in Physics with Pierre and Marie Curie, who named the new ray “radioactivity.” (Nobel Prize website)
Georg Charles de Hevesy (1885-1966)
The father of nuclear medicine is Georg de Hevesy, a Hungarian chemist who in 1923 injected a solution containing a radioactive isotope of lead into a horse-bean plant to watch its uptake in the roots, stem, leaves, and fruit. He later did a similar experiment with a rabbit, watching its circulation by the movement of the isotope. De Hevesy even experimented on himself, when he and a fellow chemist drank some radioactive water then measured its concentration in their urine. Using this data, they determined the average time a water molecule stayed in their bodies was 13 ± 1.5 days (Myers,1979).
The use of a radioactive isotope to image parts of the body became known as the Tracer Principle. This is the principle on which modern nuclear medicine is built. De Hevesy received the 1943 Nobel Prize in Chemistry for his work (Myers, 1979). He also received The Atoms for Peace Award in 1959, a prize given for peaceful application of the principles of atomic energy (MIT) and numerous honorary degrees (Myers, 1979).
Ernest Lawrence (1901-1958)
Ernest Lawrence was an American nuclear physicist who invented the cyclotron, a machine which can produce radioactive isotopes. The idea came from a diagram he found in a German physics periodical. He sketched a prototype on a napkin and then built the machine, which was small enough to fit in one hand. Once proven successful, he built larger prototypes in his lab at University of California at Berkley.
He won the 1939 Nobel Prize in Physics for his invention. The cyclotron’s ability to easily produce radioactive isotopes made the acquisition of these materials much easier for others who wished to use them for further experiments, such as his brother (see below) (Science and Technology Review).
John H. Lawrence (1903-1991)
John H. Lawrence was an American physician and also the brother of Ernest Lawrence, the inventor of the cyclotron. John Lawrence administered radioactive phosphorus to humans with leukemia and cured the disease. He was the first to use radioactive material in treating human disease (Journal of Nuclear Medicine). This method eventually became common treatment for the blood disorder polycythemia vera, a disorder that occurs when a patient has too many red blood cells in their bodies. His most famous patient with polycythemia was the Cardinal Aloysius Stepinac. For this, Dr. Lawrence received a medal from the Pope. Dr. Lawrence also used radioactive labels on blood cells to measure their life span, and even made trips to the Andes Mountains in South America to study the effects of elevation on red blood cells (Budinger, Mel, Todias, 1991).
Emilio Segrè (1905-1989)
Emilio Segre was a Jewish Italian physicist who, along with colleague Carlo Perrier, discovered the element technetium, number 43 on the periodic table. This element had not been discovered before because all of its isotopes are radioactively unstable, so the element had not previously been seen in nature on earth (Jackson, 2002). Later investigations of rock samples in Gabon, Africa have shown traces of technetium (Scerri, 2009). Advances in emission technology have shown that technetium may be present in some stars, particularly red giants. It is theorized that the stars actually produce the element (Scerri, 2009).
Segre and another colleague then discovered an isotope of technetium using Ernest Lawrence’s cyclotron, technetium-99m, which is the most commonly used radioactive isotope in nuclear medicine today. This particular isotope is useful in medicine because of its short half-life of six hours, which exposes the patient to minimal radiation, but allows enough time for measurement of its emission and for completion of imaging (Scerri, 2009).
Samuel Seidlin, MD (1895-1955)
Dr. Seidlin was an endocrinologist (specialist in diseases of the endocrine system, including diseases of the thyroid) best known for his 1943 treatment of a patient with metastatic thyroid cancer at Albert Einstein School of Medicine’s Montefiore Hospital in New York. The patient, termed B.B. in the medical literature, had had his thyroid completely removed due to thyroid cancer several years prior to his admission to Montefiore. Though he didn’t have a thyroid, B.B. exhibited all the signs of too much thyroid hormone in the body. Dr. Seidlin and his colleagues gave a tracer dose of radioactive iodine to the patient, then used a Geiger counter to determine whether the metastases showed evidence of uptake. They discovered that the metastases were, in fact, producing thyroid hormones and that there was no residual tissue from the actual thyroid left (the previous thyroid resection was successful). Therapeutic doses of radioactive iodine were administered to the patient from May to October 1943 with the result that he was effectively cured of metastatic thyroid cancer. The patient returned to normal and lived another nine years (Seidlin, 1946).
The celebrated B.B. eventually published his story in Life magazine in 1949, with pictures of him before and after treatment. There was a marked difference in the pictures, demonstrating just how ill he had been prior to Dr. Seidlin’s therapy (Siegel, 1999). This marked the first time a radioactive medication had been used to treat metastatic cancer successfully.
Benedict Cassen (1902-1972)
Benedict Cassen was the inventor of the rectilinear scanner in 1950, the first device that created images of radioactivity. The scanner used a motor to move back and forth then print images via a connection to a printer. The first model was primarily used for thyroid imaging and took one to two hours for a complete scan. Eventually, the instrument was modified for use in several body organs. The rectilinear scanner was in wide use until computed axial tomography (CT) scans were invented in the 1970s. For his invention, Cassen is considered the Father of Clinical Nuclear Medicine (Blahd, 1996).
Hal Anger (1920-2005)
Hal Anger was an American nuclear physicist who is best known for his invention of the Anger gamma camera in 1952. In contrast to Cassen’s rectilinear scanner, this camera was able to take a complete picture of a human organ, though it took over an hour to do so. Anger continued to refine the camera until it was able to take an image of radioactive tracer distribution throughout the body in much less time and demonstrated the new version to the scientific community in 1958. In 1962, Alexander Gottschalk, MD came to Anger’s laboratory to find medical applications for the new device. Dr. Gottschalk demonstrated the usefulness of the device for localizing brain tumors and showing blood flow through the heart (Tapscott, 2005).
The Anger gamma camera was the forbearer to modern PET and SPECT technology.
Allan MacLeod Cormack (1924-1998) and Godfrey Newbold Hounsfield (1919-2004)
Cormack was a South African theoretical physicist who invented computed axial tomography (CT). He designed the first successful prototype in 1963. Hounsfield was a British engineer who also built a CT scanner independent of Cormack’s research. Hounsfield took the idea a step further into the potential applications of the machine. He eventually scanned the first human brain in 1971 in a female patient suspected of having a brain tumor. The scan showed a brain cyst. The CT scanner became a commercial success and is now widely used in medicine today. Cormack and Hounsfield shared the Nobel Peace Prize in Physiology and Medicine in 1979 for their invention. Interestingly, they had never met prior to the acceptance ceremony for the prize (Cierniak, 2011).
Edward Joseph Hoffman (1942-2004) and Michael E. Phelps (1939-present)
Edward Hoffman was a nuclear chemist who, along with Michael E. Phelps and others, invented the PET scanner in 1975 at Washington University School of Medicine. A year later, the team published a paper on using the PET on the full human body. This was followed by a series of papers showing the physical principles behind PET scanning (Cherry, 2004). Michael E. Phelps helped obtain FDA approval for use of the PET and reimbursement from insurance companies, making the test more widely obtainable. Phelps started the first clinical PET center, located at UCLA. He continues to perform research and teach medical professionals how to use PET there (Society of Nuclear Medicine).
Diagnostic Nuclear Medicine Tests
Positron emission tomography (PET)
This scan uses a radiotracer that shows areas of high metabolism or high chemical activity in the body which are then picked up by the PET scanner. Areas of higher than normal metabolism are suspicious for cancer or other abnormalities. A PET is often used to stage newly diagnosed cancer (help determine whether the cancer is only in one place or whether it may have spread) or to determine whether there’s been a recurrence of previously treated cancer (Society of Nuclear Medicine and Molecular Imaging). PET scans of the brain can be used to help diagnose various brain disorders such as seizures, dementia, and Parkinson’s disease, and to determine how the brain is functioning after trauma (Johns Hopkins Medicine). PET scans of the heart can help determine how much blood is getting to the heart after a procedure to improve blood flow (Johns Hopkins Medicine).
This scan also uses a radiotracer to show function of areas of the body. The difference between SPECT and PET is in the type of radiotracers used and the type of radiation they emit. SPECT is useful for imaging of the brain, heart, and bones (National Institute of Biomedical Imaging and Bioengineering, 2016).
PET/CT
This scan combines the advantages of a CT (seeing anatomy clearly) with the advantages of a PET (seeing how the organs function) into one scan, giving doctors more information in one image. The combination of the two solved the problem many doctors had with PET alone: it was difficult to determine exactly where in the anatomy areas of increased uptake were. Combining the two allowed for more precision in planning treatment (Society of Nuclear Medicine and Molecular Imaging).
SPECT/CT
This scan combines the advantages of CT and SPECT imaging, in much the same way as a PET/CT does.
Cholescintigraphy
Also commonly called a HIDA scan, this is an imaging technique to watch how the gallbladder and bile ducts work. A radioactive tracer is injected into the arm of the patient. This is taken up by bile producing cells in the liver and travels with the bile through the gallbladder and bile ducts to the small intestine. A camera follows the progress of the tracer. This test is used to diagnose problems with the gallbladder and bile ducts (Mayo Clinic).
Bone scintigraphy
Also commonly called a bone scan, this is an imaging test specific to the skeleton. It may be used to look for fractures not easily visible on an x-ray, to help diagnose the cause of bone pain, to look for infections in the bone (called osteomyelitis), and to look for spread of cancer to the bones (Johns Hopkins).
Gastric emptying scan (GES)
This scan allows doctors to watch food as it moves through the digestive system and is primarily used in diagnosing motility disorders. Motility disorders occur when food either moves too quickly or too slowly through the digestive system. The day of the test, the patient is given a small meal to eat with radioactive tracers in it. The test occurs in several stages to accurately observe movement of the radioactive meal. It lasts about four hours from start to finish (University of Washington Medicine, 2017).
Stress/Rest Myocardial Perfusion Imaging
Also called a nuclear stress test, this test uses PET or SPECT technology to show which areas of the heart are receiving blood flow before and after exercise. This test may be ordered to make the diagnosis of heart disease, to determine how much of the heart was damaged in a recent heart attack, to see whether a patient is a good candidate for bypass surgery, or to understand how well recent treatment for heart disease is working. For the exercise portion, the patient will walk or run on a treadmill to increase the heart rate. For patients who are unable to exercise, a medication will be given to elevate the heart rate artificially. This test is usually ordered for patients with moderate to high risk of heart disease (Society of Nuclear Medicine and Molecular Imaging).
Pulmonary Ventilation/Perfusion (V/Q) Scan
This scan measures airflow and blood flow to the lungs and is used primarily to diagnose or rule out pulmonary embolus, a blood clot in the lungs. It may also be used prior to some surgeries. The V/Q scan is unique in that it uses radiotracers both injected into the arm and breathed in through a mask (National Heart, Lung, and Blood Institute, 2016).
Diseases Treated Using Nuclear Medicine
Hyperthyroidism
Hyperthyroidism is when the thyroid gland (a gland located in the neck) makes too much thyroid hormone. This causes accelerated metabolism in the body. Radioactive iodine (I-131) is a nuclear medicine therapy used to treat hyperthyroidism by destroying the overactive thyroid gland. It is administered in pill or liquid form and should not be given to pregnant or breastfeeding women. After the thyroid is destroyed, the patient will be given thyroid hormone in pill form to mimic a correctly functioning thyroid gland.
After receiving treatment, patients will be given guidelines to follow to reduce radiation exposure risk to others for the first week following treatment. Any extra radiation not used by the thyroid stays in the body for a few days following treatment and is mostly eliminated via urine. Small amounts may be eliminated in saliva, sweat, and bowel movements. Patients may set off radiation monitors at airports, border crossings, or other areas for three months after treatment (Society of Nuclear Medicine and Molecular Imaging).
Thyroid Cancer
Radioactive iodine therapy may also be used for patients with thyroid cancer. Patients will typically undergo surgery to remove the diseased thyroid prior to initiation of radioactive iodine therapy. The purpose of the radioactive iodine therapy is to make sure that all cancer cells are gone. Post treatment guidelines are similar to those of hyperthyroidism above (Society of Nuclear Medicine and Molecular Imaging).
Non-Hodgkin lymphoma
Ibritumomab tiuxetan was the first FDA approved radioimmunotherapy approach to treatment for treatment of certain types of non-Hodgkin lymphoma. This medication combines a monoclonal antibody with a radioactive particle to target cancer cells and deliver radiation. A monoclonal antibody is a laboratory designed protein which mimics a part of the body’s own immune system, called an antibody. Antibodies identify and destroy invaders, such as bacteria or viruses. The monoclonal antibody is designed to identify cancer cells and then alert the body’s immune system to destroy them. The addition of a radioactive medication allows for delivery of radiation directly to the cancer cell (Gordon, 2008).
Metastases to bones from prostate cancer
There are several targeted radionuclide therapies that help relieve pain and treat prostate cancer that has spread to the bone. These are a combination of a radioactive medication (or radionuclide) and a molecule that targets the cancer cells specifically. All are delivered in an injectable format and are designed to treat pain and help prevent fractures of bones that have metastatic lesions in them (Society of Nuclear Medicine and Molecular Imaging).
Current Research Being Done using Nuclear Medicine
Peptide Receptor Radionuclide Therapy
Peptide receptor radionuclide therapy (PRRT) is a molecular therapy that is currently in Stage III trails within the United States and the European Union. This type of therapy targets neuroendocrine carcinomas. PRRT combines a laboratory created version of a hormone which these types of tumors bind to with a radioactive medication which kills cancer cells. This allows a high dose of radiation to be delivered directly to the tumor cells with minimal harm to healthy cells, thus reducing the severity of side effects (often less than those of chemotherapy). PRRT is injected intravenously, along with some amino acids designed to protect the kidneys from effects of radiation.
PRRT offers a personalized approach to cancer treatment because it can be tailored to the characteristics of the specific tumor being targeted. It is designed to help control advanced neuroendocrine tumors (provide symptom relief, control spread of the tumor), but not cure them.
PRRT is being studied for use in certain types of lung cancer, pancreatic cancer, pheochromocytoma (rare cancer of the adrenals), carcinoids, and neuroendocrine tumors of the gastrointestinal tract. It is considered a second or third line therapy after other therapeutic options (e.g., surgery) have been exhausted or been deemed infeasible.
The current goal for research is to get this type of medication approved by the FDA. Future researchers plan to look at using more than one type of radiation therapy at the same time, other diseases this same concept could be used for, as well as other ways of delivering the medication (Society of Nuclear Medicine and Molecular Imaging).
Theranostics
This is an emerging field in the study of prostate cancer where radiotracers used in imaging are paired to a radionuclide agent to destroy cancer. Because of the radiotracer part, imaging can be performed to determine the effectiveness of the therapeutic part of the treatment. As new proteins, tumor pathways, and tumor characteristics are being discovered, research is being performed to determine whether these can be targets for future therapy (Society of Nuclear Medicine and Molecular Imaging).
Development of New Tracers
Many patients require implantation of medical devices (for example, pacemakers of the heart, or artificial knees). There is an inherent risk of bacterial infection with the use of these devices which is often not caught until it has become advanced and more difficult to treat. There is a study looking for new type of radiotracers that bacteria cells take up but human cells do not. Using PET technology to see the tracers, this would allow doctors to see infections much earlier when they are easier to treat. If successful, these tracers could be used in other types of infections as well, not just those associated with implantation of medical devices (National Institute of Biomedical Imaging and Bioengineering).
The research being done and the advances in ways nuclear medicine can help diagnose and treat illness is growing by leaps and bounds. Nuclear medicine remains an important part of modern medicine as a whole.
Scerri, E. (2009). Tales of technetium. Nature Chemistry,1(4), 332-332. doi:10.1038/nchem.271
Seidlin, S. M., Marinelli, L. D., & Oshrey, E. (1946). Radioactive Iodine Therapy: Effect on Functioning Metastases of Adenocarcinoma of the Thyroid. JAMA,132(14), 838-847.
Siegel, E. (1999). The Beginnings of Radioiodine Therapy of Metastatic Thyroid Carcinoma: A Memoir of Samuel M. Seidlin, M. D. (1895-1955) and His Celebrated Patient. Cancer Biotherapy & Radiopharmaceuticals,14(2), 71-79. doi:10.1089/cbr.1999.14.71
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