Positron emission tomography

Positron emission tomography 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, regional chemical composition, and absorption.
Different tracers are used for various imaging purposes, depending on the target process within the body, such as:

Fluorodeoxyglucose is commonly used to detect cancer.
Sodium fluoride#Medical imaging|Sodium fluoride is widely used for detecting bone formation.
Oxygen-15 -water is used to quantify myocardial blood flow.
Carbon-11 -methionine is used to image brain tumors.

PET is a common imaging technique, a medical scintillography technique used in nuclear medicine. A radiopharmaceutical—a radioisotope attached to a drug—is injected into the body as a tracer. When the radiopharmaceutical undergoes beta plus decay, a positron is emitted, and when the positron interacts with an ordinary electron, the two particles annihilate and two gamma rays are emitted in opposite directions. These gamma rays are detected by two gamma cameras to form a three-dimensional image.
PET scanners can incorporate a computed tomography scanner and are known as PET–CT scanners. PET scan images can be reconstructed using a CT scan performed using one scanner during the same session.
One of the disadvantages of a PET scanner is its high initial cost and ongoing operating costs.

Uses

PET is both a medical and research tool used in pre-clinical and clinical settings. It is used heavily in the imaging of tumors and the search for metastases within the field of clinical oncology, and for the clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias. PET is valued as a research tool to learn and enhance knowledge of the normal human brain, heart function, and support drug development. PET is also used in pre-clinical studies using animals. It allows repeated investigations into the same subjects over time, where subjects can act as their own control and substantially reduces the numbers of animals required for a given study. This approach allows research studies to reduce the sample size needed while increasing the statistical quality of its results.
Physiological processes result in anatomical changes within the body. Because PET can detect biochemical activity and the expression of certain proteins, it can provide molecular-level information long before any anatomical alterations become visible. PET achieves this by using radiolabelled molecular probes, which are taken up at varying rates depending on the tissue. Regional tracer uptake in different anatomical structures can then be visualized and approximately quantified based on the amount of injected positron-emitting tracer detected in the scan, via metrics like the standardized uptake value.
It is possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence detector. The quality of gamma-camera PET imaging is lower, and the scans take longer to acquire.
Alternative methods of medical imaging include single-photon emission computed tomography, computed tomography, magnetic resonance imaging and functional magnetic resonance imaging, and ultrasound. SPECT is an imaging technique similar to PET that uses radioligands to detect molecules in the body.

Oncology

PET scanning with the radiotracer Fluorodeoxyglucose |fluorodeoxyglucose is widely used in clinical oncology. FDG is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase. Metabolic trapping of the radioactive glucose molecule allows the PET scan to be utilized. The concentrations of imaged FDG tracer indicate tissue metabolic activity as it corresponds to the regional glucose uptake. FDG is used to explore the possibility of cancer spreading to other body sites. These FDG PET scans for detecting cancer metastasis are the most common in standard medical care. The same tracer may also be used for the diagnosis of types of dementia. Less often, other radioactive tracers, usually but not always labelled with fluorine-18, are used to image the tissue concentration of different kinds of molecules of interest inside the body.
Because the hydroxy group that is replaced by fluorine-18 to generate FDG is required for the next step in glucose metabolism in all cells, no further reactions occur in FDG. Furthermore, most tissues cannot remove the phosphate added by hexokinase. This means that FDG will remain trapped in any cell that takes it up until it decays, since phosphorylated sugars, due to their ionic charge, cannot exit from the cell. This results in intense radiolabeling of tissues with high glucose uptake, such as the normal brain, liver, kidneys, and most cancers, which have a higher glucose uptake than most normal tissue due to the Warburg effect. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin lymphoma, non-Hodgkin lymphoma, and lung cancer.
A 2020 review of research on the use of PET for Hodgkin lymphoma found evidence that negative findings in interim PET scans are linked to higher overall survival and progression-free survival; however, the certainty of the available evidence was moderate for survival, and very low for progression-free survival.
A few other isotopes and radiotracers are slowly being introduced into oncology for specific purposes. For example, ¹¹C-labelled metomidate has been used to detect tumors of adrenocortical origin. Also, fluorodopa PET/CT has proven to be a more sensitive alternative to finding and also localizing pheochromocytoma than the iobenguane scan. For prostate cancer, there is growing interest in using a PET scan with radionuclides delivered via prostate-specific membrane antigen targeting ligand, a strategy which allows imaging the primary tumor and surrounding metastases in one scan. The combination is referred to as a PSMA scan.

Neuroimaging

Neurology

PET imaging with oxygen-15 indirectly measures blood flow to the brain. In this method, increased radioactivity signal indicates increased blood flow which is assumed to correlate with increased brain activity. Because of its two-minute half-life, oxygen-15 must be piped directly from a medical cyclotron for such uses, which is difficult.
PET imaging with FDG takes advantage of the fact that the brain is normally a rapid user of glucose. Standard FDG PET of the brain measures regional glucose use and can be used in neuropathological diagnosis.
Brain pathologies such as Alzheimer's disease greatly decrease brain metabolism of both glucose and oxygen in tandem. Therefore FDG PET of the brain may also be used to successfully differentiate Alzheimer's disease from other dementing processes, and also to make early diagnoses of Alzheimer's disease. The advantage of FDG PET for these uses is its much wider availability. In addition, some other fluorine-18 based radioactive tracers can be used to detect amyloid-beta plaques, a potential biomarker for Alzheimer's in the brain. These include florbetapir, flutemetamol, Pittsburgh compound B and florbetaben.
PET imaging with FDG can also be used for localization of "seizure focus". A seizure focus will appear as hypometabolic during an interictal scan. Several radiotracers have been developed for PET that are ligands for specific neuroreceptor subtypes such as raclopride, fallypride and desmethoxyfallypride for dopamine D₂/D₃ receptors; McN5652 and DASB for serotonin transporters; mefway for serotonin 5HT_1A receptors; and nifene for nicotinic acetylcholine receptors or enzyme substrates. These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses.
PET may also be used for the diagnosis of hippocampal sclerosis, which causes epilepsy. FDG, and the less common tracers flumazenil and MPPF have been explored for this purpose. If the sclerosis is unilateral, FDG uptake can be compared with the healthy side. Even if the diagnosis is difficult with MRI, it may be diagnosed with PET.
The development of a number of novel probes for non-invasive, in-vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging close to clinical use. The earliest amyloid imaging probes included FDDNP, developed at the University of California, Los Angeles, and Pittsburgh compound B, developed at the University of Pittsburgh. These probes permit the visualization of amyloid plaques in the brains of Alzheimer's patients and could assist clinicians in making a positive clinical diagnosis of Alzheimer's disease pre-mortem and aid in the development of novel anti-amyloid therapies.
polymethylpentene is a novel radiopharmaceutical used in PET imaging to determine the activity of the acetylcholinergic neurotransmitter system by acting as a substrate for acetylcholinesterase. Post-mortem examination of Alzheimer's patients has shown decreased levels of acetylcholinesterase. PMP is used to map the acetylcholinesterase activity in the brain, which could allow for premortem diagnoses of Alzheimer's disease and assistance in monitoring treatments. Avid Radiopharmaceuticals has developed and commercialized a compound called florbetapir that uses the longer-lasting radionuclide fluorine-18 to detect amyloid plaques using PET scans.

Psychiatry and neuropsychopharmacology

Numerous compounds that bind selectively to neuroreceptors of interest in biological psychiatry have been radiolabeled with C-11 or F-18. Radioligands that bind to dopamine receptors, serotonin receptors, opioid receptors, cholinergic receptors and other sites have been used successfully in studies with human subjects. Studies have been performed examining the state of these receptors in patients compared to healthy controls in schizophrenia, substance abuse, mood disorders and other psychiatric conditions.