Nuclear medicine or nucleology is a
medical specialty
A medical specialty is a branch of medical practice that is focused on a defined group of patients, diseases, skills, or philosophy. Examples include those branches of medicine that deal exclusively with children (paediatrics), cancer (oncology), ...
involving the application of
radioactive
Radioactive decay (also known as nuclear decay, radioactivity, radioactive disintegration, or nuclear disintegration) is the process by which an unstable atomic nucleus loses energy by radiation. A material containing unstable nuclei is consi ...
substances in the
diagnosis
Diagnosis is the identification of the nature and cause of a certain phenomenon. Diagnosis is used in many different disciplines, with variations in the use of logic, analytics, and experience, to determine " cause and effect". In systems engin ...
and treatment of
disease
A disease is a particular abnormal condition that negatively affects the structure or function of all or part of an organism, and that is not immediately due to any external injury. Diseases are often known to be medical conditions that a ...
. Nuclear imaging, in a sense, is "
radiology
Radiology ( ) is the medical discipline that uses medical imaging to diagnose diseases and guide their treatment, within the bodies of humans and other animals. It began with radiography (which is why its name has a root referring to radiat ...
done inside out" because it records
radiation emitting from within the body rather than
radiation that is generated by external sources like
X-rays
An X-ray, or, much less commonly, X-radiation, is a penetrating form of high-energy electromagnetic radiation. Most X-rays have a wavelength ranging from 10 picometers to 10 nanometers, corresponding to frequencies in the range 30&nbs ...
. In addition, nuclear medicine scans differ from radiology, as the emphasis is not on imaging anatomy, but on the function. For such reason, it is called a
physiological imaging modality.
Single photon emission computed tomography
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
(SPECT) and
positron emission tomography (PET) scans are the two most common imaging modalities in nuclear medicine.
Diagnostic medical imaging
Diagnostic
In nuclear medicine imaging,
radiopharmaceuticals
Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which is ...
are taken internally, for example, through inhalation, intravenously or orally. Then, external detectors (
gamma camera
A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
s) 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.
* 2D: ''
Scintigraphy
Scintigraphy (from Latin ''scintilla'', "spark"), also known as a gamma scan, is a diagnostic test in nuclear medicine, where radioisotopes attached to drugs that travel to a specific organ or tissue (radiopharmaceuticals) are taken internally and ...
'' ("scint") is the use of internal radionuclides to create two-dimensional images.
File:Nl bone scan2.jpg, A nuclear medicine whole body bone scan. The nuclear medicine whole body bone scan is generally used in evaluations of various bone-related pathology, such as for bone pain, stress fracture, nonmalignant bone lesions, bone infections, or the spread of cancer to the bone.
File:nl mpi2.jpg, Nuclear medicine myocardial perfusion scan with thallium-201 for the rest images (bottom rows) and Tc-Sestamibi for the stress images (top rows). The nuclear medicine myocardial perfusion scan plays a pivotal role in the noninvasive evaluation of coronary artery disease. The study not only identifies patients with coronary artery disease; it also provides overall prognostic information or overall risk of adverse cardiac events for the patient.
File:parathyroid subtraction.jpg, A nuclear medicine parathyroid scan demonstrates a parathyroid adenoma adjacent to the left inferior pole of the thyroid gland. The above study was performed with Technetium-Sestamibi (1st column) and iodine-123 (2nd column) simultaneous imaging and the subtraction technique (3rd column).
File:HIDA.jpg, Normal hepatobiliary scan (HIDA scan). The nuclear medicine hepatobiliary scan is clinically useful in the detection of the gallbladder disease.
File:ventperf.jpg, Normal pulmonary ventilation and perfusion (V/Q) scan. The nuclear medicine V/Q scan is useful in the evaluation of pulmonary embolism.
File:thyroid scan.jpg, Thyroid scan with iodine-123 for evaluation of hyperthyroidism.
* 3D: ''
SPECT
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
'' 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.
File:hemangioma scan.jpg, A nuclear medicine SPECT liver scan with technetium-99m labeled autologous red blood cells. A focus of high uptake (arrow) in the liver is consistent with a hemangioma.
File:PET-MIPS-anim.gif, Maximum intensity projection (MIP) of a whole-body positron emission tomography (PET) acquisition of a 79 kg female after intravenous injection of 371 MBq of 18F-FDG (one hour prior measurement).
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-, tissue- or disease-specific (e.g.: lungs scan, heart scan, bone scan, brain scan, tumor, infection, Parkinson 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
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, ...
s or
PET/CT scans,
gallium scan
A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gal ...
s,
indium white blood cell scan
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 le ...
s,
MIBG and
octreotide scan
An octreotide scan is a type of SPECT scintigraphy used to find carcinoid, pancreatic neuroendocrine tumors, and to localize sarcoidosis. It is also called somatostatin receptor scintigraphy (SRS). Octreotide, a drug similar to somatostatin, is r ...
s.
![Iodine wb scan](https://upload.wikimedia.org/wikipedia/commons/2/2a/Iodine_wb_scan.jpg)
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
Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area ...
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 that 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
Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medical ra ...
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.
File:nl petct.jpg, Normal whole body PET/CT scan with FDG-18. The whole body PET/CT scan is commonly used in the detection, staging and follow-up of various cancers.
File:abnl petct.jpg, Abnormal whole body PET/CT scan with multiple metastases from a cancer. The whole body PET/CT scan has become an important tool in the evaluation of cancer.
Practical concerns in nuclear imaging
Although the risks of low-level radiation exposures are not well understood, a cautious approach has been universally adopted that all human radiation exposures should be kept As Low As Reasonably Practicable, "ALARP". (Originally, this was known as "As Low As Reasonably Achievable" (ALARA), but this has changed in modern draftings of the legislation to add more emphasis on the "Reasonably" and less on the "Achievable".)
Working with the ALARP principle, before a patient is exposed for a nuclear medicine examination, the benefit of the examination must be identified. This needs to take into account the particular circumstances of the patient in question, where appropriate. For instance, if a patient is unlikely to be able to tolerate a sufficient amount of the procedure to achieve a diagnosis, then it would be inappropriate to proceed with injecting the patient with the radioactive tracer.
When the benefit does justify the procedure, then the radiation exposure (the amount of radiation given to the patient) should also be kept as low as reasonably practicable. This means that the images produced in nuclear medicine should never be better than required for confident diagnosis. Giving larger radiation exposures can reduce the noise in an image and make it more photographically appealing, but if the clinical question can be answered without this level of detail, then this is inappropriate.
As a result, the radiation dose from nuclear medicine imaging varies greatly depending on the type of study. The effective radiation dose can be lower than or comparable to or can far exceed the general day-to-day environmental annual
background radiation
Background radiation is a measure of the level of ionizing radiation present in the environment at a particular location which is not due to deliberate introduction of radiation sources.
Background radiation originates from a variety of source ...
dose. Likewise, it can also be less than, in the range of, or higher than the radiation dose from an abdomen/pelvis CT scan.
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 the withholding of certain medications. Patients are encouraged to consult with the nuclear medicine department prior to a scan.
Analysis
The 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 (SPECT, or less commonly, SPET) is a nuclear medicine tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera (that is, ...
(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
Three-dimensional space (also: 3D space, 3-space or, rarely, tri-dimensional space) is a geometric setting in which three values (called ''parameters'') are required to determine the position of an element (i.e., point). This is the informa ...
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 model
A multi-compartment model is a type of mathematical model used for describing the way materials or energies are transmitted among the ''compartments'' of a system. Sometimes, the physical system that we try to model in equations is too complex, so ...
s or a
Patlak plot A Patlak plot (sometimes called Gjedde–Patlak plot, Patlak–Rutland plot, or Patlak analysis) is a graphical analysis technique based on the compartment model that uses linear regression to identify and analyze pharmacokinetics of tracers invol ...
.
Interventional nuclear medicine
Radionuclide therapy can be used to treat conditions such as
hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidis ...
,
thyroid cancer
Thyroid cancer is cancer that develops from the tissues of the thyroid gland. It is a disease in which cells grow abnormally and have the potential to spread to other parts of the body. Symptoms can include swelling or a lump in the neck. C ...
, skin cancer and blood disorders.
In nuclear medicine therapy, the radiation treatment dose is administered internally (e.g. intravenous or oral routes) or externally direct above the area to treat in form of a compound (e.g. in case of skin cancer).
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
(unsealed source) therapies
In some centers the nuclear medicine department may also use implanted capsules of isotopes (
brachytherapy
Brachytherapy is a form of radiation therapy where a sealed radiation source is placed inside or next to the area requiring treatment. ''Brachy'' is Greek for short. Brachytherapy is commonly used as an effective treatment for cervical, prost ...
) to treat cancer.
Commonly used radiation sources (radionuclides) for brachytherapy
History
The history of nuclear medicine contains contributions from 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
Oak Ridge National Laboratory (ORNL) is a U.S. multiprogram science and technology national laboratory sponsored by the U.S. Department of Energy (DOE) and administered, managed, and operated by UT–Battelle as a federally funded research an ...
for medicine-related use, in 1946.
The origins of this medical idea date back as far as the mid-1920s in
Freiburg
Freiburg im Breisgau (; abbreviated as Freiburg i. Br. or Freiburg i. B.; Low Alemannic: ''Friburg im Brisgau''), commonly referred to as Freiburg, is an independent city in Baden-Württemberg, Germany. With a population of about 230,000 (as o ...
, Germany, when
George de Hevesy
George Charles de Hevesy (born György Bischitz; hu, Hevesy György Károly; german: Georg Karl von Hevesy; 1 August 1885 – 5 July 1966) was a Hungarian radiochemist and Nobel Prize in Chemistry laureate, recognized in 1943 for his key rol ...
made experiments with radionuclides administered to rats, thus displaying metabolic pathways of these substances and establishing the
tracer principle. Possibly, the genesis of this medical field took place in 1936, when
John Lawrence, known as "the father of nuclear medicine", took a leave of absence from his faculty position at
Yale Medical School
The Yale School of Medicine is the graduate medical school at Yale University, a private research university in New Haven, Connecticut. It was founded in 1810 as the Medical Institution of Yale College and formally opened in 1813.
The primary te ...
, to visit his brother
Ernest Lawrence
Ernest Orlando Lawrence (August 8, 1901 – August 27, 1958) was an American nuclear physicist and winner of the Nobel Prize in Physics in 1939 for his invention of the cyclotron. He is known for his work on uranium-isotope separation fo ...
at his new radiation laboratory (now known as the
Lawrence Berkeley National Laboratory) in
Berkeley,
California
California is a state in the Western United States, located along the Pacific Coast. With nearly 39.2million residents across a total area of approximately , it is the most populous U.S. state and the 3rd largest by area. It is also the m ...
. Later on, John Lawrence made the first application in patients of an artificial radionuclide when he used
phosphorus-32
Phosphorus-32 (32P) is a radioactive isotope of phosphorus. The nucleus of phosphorus-32 contains 15 protons and 17 neutrons, one more neutron than the most common isotope of phosphorus, phosphorus-31. Phosphorus-32 only exists in small quantiti ...
to treat
leukemia
Leukemia ( also spelled leukaemia and pronounced ) is a group of blood cancers that usually begin in the bone marrow and result in high numbers of abnormal blood cells. These blood cells are not fully developed and are called ''blasts'' or ...
.
Many historians consider the discovery of artificially produced radionuclides by
Frédéric Joliot-Curie
Jean Frédéric Joliot-Curie (; ; 19 March 1900 – 14 August 1958) was a French physicist and husband of Irène Joliot-Curie, with whom he was jointly awarded the Nobel Prize in Chemistry in 1935 for their discovery of Induced radioactivity. T ...
and
Irène Joliot-Curie
Irène Joliot-Curie (; ; 12 September 1897 – 17 March 1956) was a French chemist, physicist and politician, the elder daughter of Pierre and Marie Curie, and the wife of Frédéric Joliot-Curie. Jointly with her husband, Joliot-Curie was awar ...
in 1934 as the most significant milestone in nuclear medicine.
In February 1934, they reported the first artificial production of radioactive material in the journal
''Nature'', 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
Antoine Henri Becquerel (; 15 December 1852 – 25 August 1908) was a French engineer, physicist, Nobel laureate, and the first person to discover evidence of radioactivity. For work in this field he, along with Marie Skłodowska-Curie and Pie ...
for radioactive uranium salts, and
Marie Curie
Marie Salomea Skłodowska–Curie ( , , ; born Maria Salomea Skłodowska, ; 7 November 1867 – 4 July 1934) was a Polish and naturalized-French physicist and chemist who conducted pioneering research on radioactivity. She was the first ...
(mother of Irène Curie) for radioactive thorium, polonium and coining the term "radioactivity."
Taro Takemi studied the application of
nuclear physics
Nuclear physics is the field of physics that studies atomic nuclei and their constituents and interactions, in addition to the study of other forms of nuclear matter.
Nuclear physics should not be confused with atomic physics, which studies the ...
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 when on May 11, 1946, an article in the Journal of the American Medical Association (JAMA) by Massachusetts General Hospital's Dr.
Saul Hertz
Saul Hertz, M.D. (April 20, 1905 – July 28, 1950) was an American physician who devised the medical uses of radioactive iodine. Hertz pioneered the first targeted cancer therapies. Hertz is called the father of the field of theranostics, combini ...
and Massachusetts Institute of Technology's Dr.Arthur Roberts, described the successful use of treating Graves' Disease with radioactive iodine (RAI) was published.
Additionally,
Sam Seidlin.
brought further development in the field describing a successful treatment of a patient with thyroid cancer metastases using radioiodine (
I-131). These articles are considered by many historians as the most important articles ever published in nuclear medicine.
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. Among the many radionuclides that were discovered for medical-use, none were as important as the discovery and development of
Technetium-99m
Technetium-99m (99mTc) is a metastable nuclear isomer of technetium-99 (itself an isotope of technetium), symbolized as 99mTc, that is used in tens of millions of medical diagnostic procedures annually, making it the most commonly used medical ra ...
. 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 a
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.
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
Benedict may refer to:
People Names
*Benedict (given name), including a list of people with the given name
*Benedict (surname), including a list of people with the surname
Religious figures
* Pope Benedict I (died 579), head of the Catholic Chu ...
in developing the first
rectilinear scanner and
Hal O. Anger's scintillation camera (
Anger camera
A gamma camera (γ-camera), also called a scintillation camera or Anger camera, is a device used to image gamma radiation emitting radioisotopes, a technique known as scintigraphy. The applications of scintigraphy include early drug development ...
) broadened the young discipline of nuclear medicine into a full-fledged medical imaging specialty.
By the early 1960s, in southern
Scandinavia
Scandinavia; Sámi languages: /. ( ) is a subregion in Northern Europe, with strong historical, cultural, and linguistic ties between its constituent peoples. In English usage, ''Scandinavia'' most commonly refers to Denmark, Norway, and Swe ...
,
Niels A. Lassen,
David H. Ingvar, and
Erik Skinhøj developed techniques that provided the first blood flow maps of the brain, which initially involved
xenon-133
Naturally occurring xenon (54Xe) consists of seven stable isotopes and two very long-lived isotopes. Double electron capture has been observed in 124Xe (half-life ) and double beta decay in 136Xe (half-life ), which are among the longest measured ...
inhalation; an intra-arterial equivalent was developed soon after, enabling measurement of the local distribution of cerebral activity for patients with
neuropsychiatric
Neuropsychiatry or Organic Psychiatry is a branch of medicine that deals with psychiatry as it relates to neurology, in an effort to understand and attribute behavior to the interaction of neurobiology and social psychology factors. Within neurop ...
disorders such as schizophrenia. Later versions would have 254
scintillators so a two-dimensional image could be produced on a color monitor. It allowed them to construct images reflecting brain activation from speaking, reading, visual or auditory perception and voluntary movement. The technique was also used to investigate, e.g., imagined sequential movements, mental calculation and mental spatial navigation.
By the 1970s most organs of the body could be visualized using nuclear medicine procedures. In 1971,
American Medical Association
The American Medical Association (AMA) is a professional association and lobbying group of physicians and medical students. Founded in 1847, it is headquartered in Chicago, Illinois. Membership was approximately 240,000 in 2016.
The AMA's sta ...
officially recognized nuclear medicine as a medical specialty.
In 1972, the
American Board of Nuclear Medicine
The American Board of Nuclear Medicine (ABNM) certifies physicians as specialists in the practice of nuclear medicine. Diplomates of the ABNM are called nuclear medicine physicians. The ABNM is one of the 24 member boards of the American Board ...
was established, and in 1974, the
American Osteopathic Board of Nuclear Medicine was established, cementing nuclear medicine as a stand-alone medical specialty.
In the 1980s, radiopharmaceuticals were designed for use in diagnosis of heart disease. The development of single photon emission computed tomography (SPECT), 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
A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive appearances, intelligence ...
). 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. 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.
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, which also was facilitated by establishing 18F-labelled tracers for standard procedures, allowing work at non-cyclotron-equipped sites. PET/CT imaging is now an integral part of oncology for diagnosis, staging and treatment monitoring. A fully integrated MRI/PET scanner is on the market from early 2011.
Sources of radionuclides
99mTc is normally supplied to hospitals through a
radionuclide generator
A radionuclide generator is a device which provides a local supply of a short-lived radioactive substance from the decay of a longer-lived parent radionuclide. They are commonly used in nuclear medicine to supply a radiopharmacy. The generator prov ...
containing the parent radionuclide
molybdenum-99
Molybdenum (42Mo) has 33 known isotopes, ranging in atomic mass from 83 to 115, as well as four metastable nuclear isomers. Seven isotopes occur naturally, with atomic masses of 92, 94, 95, 96, 97, 98, and 100. All unstable isotopes of molybdenum ...
.
99Mo is
typically obtained as a fission product of
235U in nuclear reactors, however global supply shortages have led to the exploration of
other methods of production. About a third of the world's supply, and most of Europe's supply, of medical isotopes is produced at the
Petten nuclear reactor
The Petten High Flux Reactor (HFR), is a nuclear research reactor located in Petten, The Netherlands. The HFR is on the premises of the Petten research centre and it is a high flux reactor. It is owned by the Joint Research Centre (JRC) and manage ...
in the
Netherlands
)
, anthem = ( en, "William of Nassau")
, image_map =
, map_caption =
, subdivision_type = Sovereign state
, subdivision_name = Kingdom of the Netherlands
, established_title = Before independence
, established_date = Spanish Netherl ...
. Another third of the world's supply, and most of North America's supply, was produced at the
Chalk River Laboratories
Chalk River Laboratories (french: Laboratoires de Chalk River; also known as CRL, Chalk River Labs and formerly Chalk River Nuclear Laboratories, CRNL) is a Canadian nuclear research facility in Deep River, about north-west of Ottawa.
CRL is ...
in
Chalk River,
Ontario
Ontario ( ; ) is one of the thirteen provinces and territories of Canada.Ontario is located in the geographic eastern half of Canada, but it has historically and politically been considered to be part of Central Canada. Located in Central C ...
, Canada until its permanent shutdown in 2018.
The most commonly used radioisotope in PET
18F, is not produced in any nuclear reactor, but rather in a circular accelerator called a
cyclotron
A cyclotron is a type of particle accelerator invented by Ernest O. Lawrence in 1929–1930 at the University of California, Berkeley, and patented in 1932. Lawrence, Ernest O. ''Method and apparatus for the acceleration of ions'', filed: Jan ...
. The cyclotron is used to accelerate
protons to bombard the stable heavy isotope of oxygen
18O. The
18O constitutes about 0.20% of ordinary
oxygen
Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...
(mostly
oxygen-16
Oxygen-16 (16O) is a stable isotope of oxygen, having 8 neutrons and 8 protons in its nucleus. It has a mass of . Oxygen-16 is the most abundant isotope of oxygen and accounts for 99.762% of oxygen's natural abundance. The relative and absol ...
), from which it is extracted. The
18F is then typically used to make
FDG.
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
Microencapsulation is a process in which tiny particles or droplets are surrounded by a coating to give small capsules, with useful properties. In general, it is used to incorporate food ingredients, enzymes, cells or other materials on a micro ...
. Some studies require the labeling of a patient's own blood cells with a radionuclide (
leukocyte scintigraphy and
red blood cell
Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...
scintigraphy). Most diagnostic radionuclides emit
gamma ray
A gamma ray, also known as gamma radiation (symbol γ or \gamma), is a penetrating form of electromagnetic radiation arising from the radioactive decay of atomic nuclei. It consists of the shortest wavelength electromagnetic waves, typically ...
s either directly from their decay or indirectly through
electron–positron annihilation
Electron–positron annihilation occurs when an electron () and a positron (, the electron's antiparticle) collide. At low energies, the result of the collision is the annihilation of the electron and positron, and the creation of energetic photo ...
, while the cell-damaging properties of
beta particles
A beta particle, also called beta ray or beta radiation (symbol β), is a high-energy, high-speed electron or positron emitted by the radioactive decay of an atomic nucleus during the process of beta decay. There are two forms of beta decay, β ...
are used in therapeutic applications. Refined radionuclides for use in nuclear medicine are derived from
fission or fusion processes in
nuclear reactor
A nuclear reactor is a device used to initiate and control a fission nuclear chain reaction or nuclear fusion reactions. Nuclear reactors are used at nuclear power plants for electricity generation and in nuclear marine propulsion. Heat fr ...
s, which produce radionuclides with longer half-lives, or
cyclotron
A cyclotron is a type of particle accelerator invented by Ernest O. Lawrence in 1929–1930 at the University of California, Berkeley, and patented in 1932. Lawrence, Ernest O. ''Method and apparatus for the acceleration of ions'', filed: Jan ...
s, which produce radionuclides 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, iodine-123, iodine-131, thallium-201, gallium-67, fluorine-18
fluorodeoxyglucose
18F.html" ;"title="sup>18F">sup>18Fluorodeoxyglucose ( INN), or fluorodeoxyglucose F 18 (USAN and USP), also commonly called fluorodeoxyglucose and abbreviated 18F.html" ;"title="sup>18F">sup>18FDG, 2- 18F.html" ;"title="sup>18F">sup>18FDG or ...
, and indium-111 labeled
leukocytes. The most commonly used gaseous/aerosol radionuclides are xenon-133, krypton-81m, (
aerosolised) technetium-99m.
Policies and procedures
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 dose delivered to a patient in a nuclear medicine investigation, though unproven, is generally accepted to 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, and dosage amounts are typically significantly higher than those of X-rays.
The radiation dose from a nuclear medicine investigation is expressed as an
effective dose with units of
sievert
The sievert (symbol: SvNot be confused with the sverdrup or the svedberg, two non-SI units that sometimes use the same symbol.) is a unit in the International System of Units (SI) intended to represent the stochastic health risk of ionizing rad ...
s (usually given in millisieverts, mSv). The effective dose resulting from an investigation is influenced by the amount of radioactivity administered in mega
becquerel
The becquerel (; symbol: Bq) is the unit of radioactivity in the International System of Units (SI). One becquerel is defined as the activity of a quantity of radioactive material in which one nucleus decays per second. For applications relatin ...
s (MBq), the
physical properties of the
radiopharmaceutical
Radiopharmaceuticals, or medicinal radiocompounds, are a group of pharmaceutical drugs containing radioactive isotopes. Radiopharmaceuticals can be used as diagnostic and therapeutic agents. Radiopharmaceuticals emit radiation themselves, which ...
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
Renal functions include maintaining an acid–base balance; regulating fluid balance; regulating sodium, potassium, and other electrolytes; clearing toxins; absorption of glucose, amino acids, and other small molecules; regulation of blood pre ...
to 11.2 mSv (11,200 μSv) for a 80 MBq
thallium
Thallium is a chemical element with the symbol Tl and atomic number 81. It is a gray post-transition metal that is not found free in nature. When isolated, thallium resembles tin, but discolors when exposed to air. Chemists William Crookes an ...
-201
myocardial imaging procedure. The common bone scan with 600 MBq of technetium-99m
MDP has an effective dose of approximately 2.9 mSv (2,900 μSv).
Formerly, units of measurement were the
curie
In computing, a CURIE (or ''Compact URI'') defines a generic, abbreviated syntax for expressing Uniform Resource Identifiers (URIs). It is an abbreviated URI expressed in a compact syntax, and may be found in both XML and non-XML grammars. A CURIE ...
(Ci), being 3.7E10 Bq, and also 1.0
gram
The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram.
Originally defined as of 1795 as "the absolute weight of a volume of pure water equal to th ...
s of
Radium
Radium is a chemical element with the symbol Ra and atomic number 88. It is the sixth element in group 2 of the periodic table, also known as the alkaline earth metals. Pure radium is silvery-white, but it readily reacts with nitrogen (rathe ...
(
Ra-226); the
rad (radiation absorbed dose), now replaced by the
gray
Grey (more common in British English) or gray (more common in American English) is an intermediate color between black and white. It is a neutral or achromatic color, meaning literally that it is "without color", because it can be composed o ...
; and the rem (
Röntgen equivalent man
The roentgen equivalent man (rem) is a CGS unit of equivalent dose, effective dose, and committed dose, which are dose measures used to estimate potential health effects of low levels of ionizing radiation on the human body.
Quantities measur ...
), now replaced with the
sievert
The sievert (symbol: SvNot be confused with the sverdrup or the svedberg, two non-SI units that sometimes use the same symbol.) is a unit in the International System of Units (SI) intended to represent the stochastic health risk of ionizing rad ...
. The rad and rem are essentially equivalent for almost all nuclear medicine procedures, and only
alpha radiation
Alpha decay or α-decay is a type of radioactive decay in which an atomic nucleus emits an alpha particle (helium nucleus) and thereby transforms or 'decays' into a different atomic nucleus, with a mass number that is reduced by four and an at ...
will produce a higher Rem or Sv value, due to its much higher
Relative Biological Effectiveness
In radiobiology, the relative biological effectiveness (often abbreviated as RBE) is the ratio of biological effectiveness of one type of ionizing radiation relative to another, given the same amount of absorbed energy. The RBE is an empirica ...
(RBE). Alpha emitters are nowadays rarely used in nuclear medicine, but were used extensively before the advent of nuclear reactor and accelerator produced radionuclides. The concepts involved in radiation exposure to humans are covered by the field of
Health Physics
Health physics, also referred to as the science of radiation protection, is the profession devoted to protecting people and their environment from potential radiation hazards, while making it possible to enjoy the beneficial uses of radiation. H ...
; the development and practice of safe and effective nuclear medicinal techniques is a key focus of
Medical Physics
Medical physics deals with the application of the concepts and methods of physics to the prevention, diagnosis and treatment of human diseases with a specific goal of improving human health and well-being. Since 2008, medical physics has been incl ...
.
Regulatory frameworks and guidelines
Different countries around the world maintain regulatory frameworks that are responsible for the management and use of radionuclides in different medical settings. For example, in the US, the
Nuclear Regulatory Commission (NRC) and the
Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) have guidelines in place for hospitals to follow. With the NRC, if radioactive materials aren't involved, like X-rays for example, they are not regulated by the agency and instead are regulated by the individual states. International organizations, such as the
International Atomic Energy Agency (IAEA), have regularly published different articles and guidelines for best practices in nuclear medicine as well as reporting on emerging technologies in nuclear medicine. Other factors that are considered in nuclear medicine include a patient's medical history as well as post-treatment management. Groups like
International Commission on Radiological Protection
The International Commission on Radiological Protection (ICRP) is an independent, international, non-governmental organization, with the mission to protect people, animals, and the environment from the harmful effects of ionising radiation. Its r ...
have published information on how to manage the release of patients from a hospital with unsealed radionuclides.
See also
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Human subject research
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List of Nuclear Medicine Societies
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Nuclear medicine physician
Nuclear medicine physicians, also called nuclear radiologists or simply nucleologists, are medical specialists that use tracers, usually radiopharmaceuticals, for diagnosis and therapy. Nuclear medicine procedures are the major clinical applicati ...
*
Nuclear pharmacy
Nuclear pharmacy, also known as radiopharmacy, involves preparation of radioactive materials for patient administration that will be used to diagnose and treat specific diseases in nuclear medicine. It generally involves the practice of combining ...
*
Nuclear technology
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Radiographer
Radiographers, also known as radiologic technologists, diagnostic radiographers and medical radiation technologists are healthcare professionals who specialize in the imaging of human anatomy for the diagnosis and treatment of pathology. Radi ...
References
Further reading
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External links
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Solving the Medical Isotope CrisisHearing before the Subcommittee on Energy and Environment of the Committee on Energy and Commerce, House of Representatives, One Hundred Eleventh Congress, First Session, September 9, 2009
{{Authority control
Radiology
Medicinal radiochemistry