Introduction

Nuclear medicine is conducted by administering small doses of radioactive material to a patient and then using a device, gamma cameras, to detect the location of the material. There are a variety of radiotracers that can be given to a patient either through injection, inhalation, or ingestion. The most commonly used radiotracers include indium-111, technetium-99m, gallium-67, and fluorodeoxyglucose. All of these materials emit gamma radiation, which is picked up by an imaging device to determine a specific function of the patient’s body.[1][2] Depending on which radiotracer is used, the radioactive material will be eliminated from the patient’s body by either the lungs, urine, or stool within hours to days.[3] 

The process of administering radiotracers into the patient, instead of from an external source, is referred to as endoradiology. Nuclear medicine differs from other imaging studies because it can show the anatomic structures of the body and the function of organs. It can even show processes down to the molecular and cellular level, such as blood flow, cellular metabolism, expression of cell receptors, and more.[1][2][4]

Specimen Collection

Various specimens may need to be collected for nuclear medicine scans. In vitro methods for blood samples include drawing blood from the patient, commonly in the arm. The blood is then mixed with the appropriate radiotracer. Depending on the radiotracer, information can be obtained from the blood sample, or the sample needs to be injected back into the patient.[1] The most common use of in vitro blood samples is to determine red blood cell mass.

Another common use of in vitro nuclear medicine includes a urea breath test. A patient will ingest a radiotracer pill and breath through a straw into a balloon to capture air from the lungs. The air is then assessed for increased labeled 14CO2 in the patient’s breath.[5]

There are less common uses of in vitro nuclear medicine. Some of these processes include the need to collect fluid and tissue samples. Any specimen collection must be completed through a sterile process.

Procedures

The most common uses for nuclear medicine include examining the kidneys, thyroid, heart, brain, bones, and breasts. Procedures can be broken down into in vivo and in vitro studies. In vitro studies are less common and include taking a sample from the patient, most commonly a blood sample, and assessing it through nuclear medicine outside of the patient’s body. In vivo methods are more commonly used. In these studies, radiotracer material is given to the patient through injection, consumption, or inhalation, depending on the specific type of study. After administration of the radioactive material, a gamma camera takes photographs of the patient.

The images can either be two or three-dimensional. Two-dimensional images are obtained from a stationary gamma camera. Three-dimensional images are produced either through single-photon emission computed tomography (SPECT) or Positron Emission Tomography (PET). SPECT uses a gamma camera that rotates around the patient to create a three-dimensional image.  PET uses the radioisotope fluorine-18, which releases positrons that are captured by the camera. This image has better spatial resolution and contrast. The images are compared to evaluate the activity at the organ, tissue, or cell level.[4]

Indications

Indications for nuclear medicine include assessing organs' function, detecting cancers, and identifying rejection of a transplant, diagnosis, or treatment.

Common indications include:

Heart

• Visualize myocardial perfusion.
• Assess cardiac function.
• Calculate the ejection fraction.

Lungs

• Evaluate lung perfusion.
• Assess lung function.
• Diagnose a pulmonary embolism.

Genitourinary

• Evaluate renal perfusion.
• Detect renal obstructions.
• Discover vesicourethral reflux.

Bones

• Detect diseases such as osteomyelitis or Paget’s disease.
• Evaluate spondylolisthesis.
• Evaluate osteopathies such as fractures.

Thyroid

• Determine thyroid size.
• Treat hyperthyroidism.
• Detect hypothyroidism.
• Locate ectopic thyroid tissue.

Gastrointestinal

• Determine the gastric emptying time to detect anatomical obstruction or delayed emptying time.
• Evaluate esophageal motility.
• Identify a gastrointestinal bleed.
• Locate Meckel’s diverticulum.
• Detect hepatic lesions.

Brain

• Evaluate blood flow to the brain.
• Follow up on the response to treatment to infection.

Potential Diagnosis

Cancers can be diagnosed and staged by nuclear medicine scans. Cancer cells uptake more glucose than normal cells. Thus, when fluorine-18-fluorodeoxyglucose is given to a patient, it will accumulate in cancer cells. The limitations of this include organs that have lower metabolic activities, such as the prostate and liver. This has led to the creation of the radiotracers carbon-11 methyl-methionine, fluorine-18-fluoro-l-phenylalanine, and fluorine-18-fluoro-L-thymidine, which detect DNA synthesis and metabolism of amino acids. These can help detect cancers that are not as well detected by fluorine-18-fluorodeoxyglucose, such as cancers in the brain.[4]

Nuclear medicine can also be used to detect inflammation and infection. The radiotracers indium-111 and technetium-99m are tagged onto a patient’s white blood cells. The mixture of tagged white blood cells is injected back into the patient, and these white blood cells travel to areas of inflammation and infection. A scintillation camera is used to detect which areas the white blood cells travel to, indicating infection. Other ways to detect infection include using nanomaterials that target monocytes and macrophages. The phagocytic properties of these cells allow them to uptake the nanoparticles. Increased activity is shown in areas where there is increased uptake of the nanoparticles.[1][6] 

Decreased glucose uptake in certain parts of brain tissue is seen in neurodegenerative disorders. Scanning the brain after injection of fluorine-18-fluorodeoxyglucose allows one to see the glucose metabolism of the brain. In healthy individuals, the entire cerebral cortex will show glucose metabolism. Patients with Alzheimer’s disease will show decreased glucose metabolism in certain parts of the brain.[4]

Radiotracers can diagnose perfusion deficits. A patient’s red blood cells are tagged with radiotracers and injected back into the bloodstream. Detecting where the blood cells go and their pattern of movement can diagnose coronary artery disease. This is not limited to the heart. Other organs such as the kidneys, gastrointestinal tract, and lungs can all have their perfusion assessed via nuclear medicine.[7] 

Nuclear medicine shows promise with the diagnosis of coronary atherosclerosis. A few studies have shown that fluorine-18-fluorodeoxyglucose has increased uptake in areas of atherosclerotic lesions such as in the carotid arteries.[7][8]

Gastrointestinal functionality can be assessed by nuclear medicine. Radiotracers are mixed into liquid egg whites and cooked to an omelet consistency. This is eaten by the patient, and the movement of the food is captured by a gamma camera.[9][10] 

Other diagnoses can be made about endocrine functionality, such as assessing thyroid functionality. A radioactive iodine uptake test using I-123 or I-131 is given to the patient, and the thyroid function is assessed to give the patient a diagnosis of hyperthyroidism.[11]

Normal and Critical Findings

Depending on the study chosen, there are different normal and critical findings found in nuclear medicine. Normal findings arise when radiotracer is injected and interacts with the body in a predictable pattern. For example, in a bone scan, the radiotracer's uptake into bones should be symmetrical throughout the skeleton, with exceptions in the acromioclavicular joints and sacroiliac joints, a slight increase of uptake should be expected.[12] Critical findings arise when the radiotracer does not behave in the expected fashion. It is important to know the different possible results of the study to interpret the findings accurately.

Interfering Factors

SPECT imaging can produce false results from an assortment of imaging artifacts. These include movement from the patient, cardiac motion, attenuation of photon beams, and misalignment of the attenuation maps. The software has been developed to help diminish the effect of these artifacts. Some clinicians will repeat the study with the patient positioned prone, supine, or standing to better recognize artifacts.[13]

Other interfering factors can include improper elimination of the radiotracer. Some studies require that once the radiotracer is given, it is bound to the appropriate site, and the rest is eliminated via the kidneys or liver. If there is improper elimination, then the radiotracer can be picked up in areas that obscure the results.[14][3]

Tc99m labeled radiotracers have the unique interfering factor of unbending, resulting in unbound Tc99m-pertechnetate. The free Tc99m will travel around the patient’s body and eventually localize to the salivary glands, thyroid, and stomach. This may skew the interpretation of studies using this radiotracer.[12][15]

Studies requiring detection of radiotracer inside the patient can be obscured if the patient is wearing jewelry. It is recommended that all jewelry be removed before the procedure.

Medications can also interfere with the results. Depending on the study being performed, it may be recommended that certain medications be held. For example, for radioactive iodine I-131 therapy, it is recommended that the patient does not take anti-thyroid medication such as propylthiouracil or methimazole one to two weeks before the procedure.[16]

Complications

Nuclear medicine procedures are generally considered safe. The most common risk factors include an allergic reaction to the radiotracer or an injection site reaction.

Complications could include

• Incomplete administration of the radiotracer. Either from not injecting, eating, or inhaling enough of the radiotracer.
• Diabetic hyperglycemia over 250 mg/dL. This can cause incomplete results for studies requiring ingestion of the radiotracer.[10]
• Glove phenomenon- Contrast for a bone-imaging agent, is injected into the radial artery, and the bones take up more radiotracer in the palm and thumb due to blood flow.[17]
• Urinary tract infection after performing a retrograde radionuclide cystography.[18]

Side effects of nuclear medicine studies include

• An allergic reaction to the food when eating a meal containing the radiotracer, such as egg whites.
• It is rare to have an adverse reaction to radiotracers. If a reaction does occur, it is most commonly a mild rash. A study found that an adverse reaction to radiotracers during 783,525 administrations only occurred in 0.0023% of participants.[19]

Patient Safety and Education

It is important that before any nuclear medicine study is conducted, patients are educated on the procedure, the risks involved, and the preparation needed for the study. Nuclear medicine uses ionizing radiation from the radiotracers administered to the patient. The amount of radiation a patient receives depends on the study being conducted and what radiotracer is injected. If the effective dose of radiation is <0.1 mSv, then the dose is considered trivial. This includes studies of glomerular filtration rate, which use about .006 mSv of radiation. Studies like thyroid scans use about 0.14 mSv and are considered intermediate since the radiation dose is between 0.1 and 1 mSv. A dose between 1 and 10 mSv is considered intermediate. A nuclear bone scan uses about 4 mSv, placing it in the intermediate range.[12] 

Any dose of radiation above 10 mSv is considered moderate. Many therapeutic nuclear medicine procedures are in this category. For reference, the amount of radiation an average person receives in a day is about 3 mSv.[20][21]

Adverse effects of radiotracers are very uncommon. One study found that out of 783,525 radiotracer injections, only 18 patients had an adverse reaction to the radiotracer. This equates to an incidence of 0.0023%.[19]

Many different studies can be used for nuclear medicine, and patient education will differ depending on the type that needs to be completed. Common topics to educate patients on include avoiding taking certain medications. For some studies, patients should avoid eating food or drinking carbonated drinks before the procedure.[22] Other studies may require patients to avoid smoking. Women who are breastfeeding may need to avoid feeding for 12 to 24 hours, depending on the radiotracer.[12]

Clinical Significance

While there are many tools used to evaluate a patient's anatomy, there are fewer tools to assess physiological function. Nuclear medicine can do both. While the images captured from nuclear medicine might not be as high of a resolution as images from computed tomography or magnetic resonance imaging, they can still be more sensitive for some indications. There is a wide range of uses for nuclear medicine, and new radiotracers are continually being developed. This presents a challenge to clinicians when sending patients for testing. Many patients who would benefit from these studies are not referred to have the study completed due to a clinician's lack of knowledge about the procedures.[23] 

Nuclear medicine has effective uses for myocardial perfusion imaging, detecting bone malignancies, detecting renal outflow obstruction, assessing thyroid nodules, detecting pulmonary embolisms, and more. Due to the nature of nuclear medicine, it can even be used to treat disorders such as hyperthyroidism and neural crest tumors.[16][23]