Positron emission tomography

Positron Emission Tomography
ECAT-Exact-HR--PET-Scanner.jpg
Image of a typical positron emission tomography (PET) facility
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Positron-emission tomography (PET)[1] is a nuclear medicine functional imaging technique that is used to observe metabolic processes in the body as an aid to the diagnosis of disease. The system detects pairs of gamma rays emitted indirectly by a positron-emitting radionuclide, most commonly fluorine-18, which is introduced into the body on a biologically active molecule called a radioactive tracer. Three-dimensional images of tracer concentration within the body are then constructed by computer analysis. In modern PET-CT scanners, three-dimensional imaging is often accomplished with the aid of a CT X-ray scan performed on the patient during the same session, in the same machine.

If the biologically active tracer molecule chosen for PET is fludeoxyglucose (FDG), an analogue of glucose, the concentrations of tracer imaged will indicate tissue metabolic activity as it corresponds to the regional glucose uptake. Use of this tracer to explore the possibility of cancer metastasis (i.e., spreading to other sites) is the most common type of PET scan in standard medical care (representing 90% of current scans). Metabolic trapping of the radioactive glucose molecule allows the PET scan to be utilized.[2] The same tracer may also be used for PET investigation and diagnosis of types of dementia. Less often, other radioactive tracers, usually but not always labeled with fluorine-18, are used to image the tissue concentration of other types of molecules of interest.

One of the disadvantages of PET scanners is their operating cost.[3]

Uses

PET/CT-System with 16-slice CT; the ceiling mounted device is an injection pump for CT contrast agent

PET is both a medical and research tool. It is used heavily in clinical oncology (medical imaging of tumours and the search for metastases), and for clinical diagnosis of certain diffuse brain diseases such as those causing various types of dementias. PET is also an important research tool to map normal human brain and heart function, and support drug development.

PET is also used in pre-clinical studies using animals, where it allows repeated investigations into the same subjects. This is particularly valuable in cancer research, as it results in an increase in the statistical quality of the data (subjects can act as their own control) and substantially reduces the numbers of animals required for a given study.

Alternative methods of scanning include x-ray computed tomography (CT), magnetic resonance imaging (MRI) and functional magnetic resonance imaging (fMRI), ultrasound and single-photon emission computed tomography (SPECT).

While some imaging scans such as CT and MRI isolate organic anatomic changes in the body, PET and SPECT are capable of detecting areas of molecular biology detail (even prior to anatomic change). PET scanning does this using radiolabelled molecular probes that have different rates of uptake depending on the type and function of tissue involved. Changing of regional blood flow in various anatomic structures (as a measure of the injected positron emitter) can be visualized and relatively quantified with a PET scan.

PET imaging is best performed using a dedicated PET scanner. It is also possible to acquire PET images using a conventional dual-head gamma camera fitted with a coincidence detector. Although the quality of gamma-camera PET is considerably lower and acquisition is slower, this method allows institutions with low demand for PET to provide on-site imaging, instead of referring patients to another centre or relying on a visit by a mobile scanner.

Oncology

Whole-body PET scan using 18F-FDG. The normal brain and kidneys are labeled, and radioactive urine from breakdown of the FDG is seen in the bladder. In addition, a large metastatic tumor mass from colon cancer is seen in the liver.

PET scanning with the tracer fluorine-18 (F-18) fluorodeoxyglucose (FDG), called FDG-PET, is widely used in clinical oncology. This tracer is a glucose analog that is taken up by glucose-using cells and phosphorylated by hexokinase (whose mitochondrial form is greatly elevated in rapidly growing malignant tumors). A typical dose of FDG used in an oncological scan has an effective radiation dose of 14 mSv.[4] Because the oxygen atom that is replaced by F-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 (with the notable exception of liver and kidneys) cannot remove the phosphate added by hexokinase. This means that FDG is 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. As a result, FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers, particularly in Hodgkin's lymphoma, non-Hodgkin lymphoma, and lung cancer.[citation needed]

A few other isotopes and radiotracers are slowly being introduced into oncology for specific purposes. For example, 11C-labelled metomidate (11C-metomidate), has been used to detect tumors of adrenocortical origin.[5][6] Also, FDOPA PET/CT (or F-18-DOPA PET/CT), in centers which offer it, has proven to be a more sensitive alternative to finding, and also localizing, pheochromocytoma than the MIBG scan.[7][8][9]

Neuroimaging

PET scan of the human brain
  • Neurology: PET neuroimaging is based on an assumption that areas of high radioactivity are associated with brain activity. What is actually measured indirectly is the flow of blood to different parts of the brain, which is, in general, believed to be correlated, and has been measured using the tracer oxygen-15. Because of its 2-minute half-life, O-15 must be piped directly from a medical cyclotron for such uses, which is difficult. In practice, since the brain is normally a rapid user of glucose, and since brain pathologies such as Alzheimer's disease greatly decrease brain metabolism of both glucose and oxygen in tandem, standard FDG-PET of the brain, which measures regional glucose use, may also be successfully used to 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. 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 (i.e. radioligands) have been developed for PET that are ligands for specific neuroreceptor subtypes such as [11C] raclopride, [18F] fallypride and [18F] desmethoxyfallypride for dopamine D2/D3 receptors, [11C] McN 5652 and [11C] DASB for serotonin transporters, [18F] Mefway for serotonin 5HT1A receptors, [18F] Nifene for nicotinic acetylcholine receptors or enzyme substrates (e.g. 6-FDOPA for the AADC enzyme). These agents permit the visualization of neuroreceptor pools in the context of a plurality of neuropsychiatric and neurologic illnesses.
The development of a number of novel probes for noninvasive, in vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging to the doorstep of clinical use. The earliest amyloid imaging probes included 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP)[10] developed at the University of California, Los Angeles and N-methyl-[11C]2-(4'-methylaminophenyl)-6-hydroxybenzothiazole[11] (termed Pittsburgh compound B) developed at the University of Pittsburgh. These amyloid imaging 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 AD pre-mortem and aid in the development of novel anti-amyloid therapies. [11C]PMP (N-[11C]methylpiperidin-4-yl propionate) 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 AD patients have shown decreased levels of acetylcholinesterase. [11C]PMP is used to map the acetylcholinesterase activity in the brain, which could allow for pre-mortem diagnoses of AD and help to monitor AD treatments.[12] 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.[13]

Cardiology

Cardiology, atherosclerosis and vascular disease study: In clinical cardiology, FDG-PET can identify so-called "hibernating myocardium", but its cost-effectiveness in this role versus SPECT is unclear. FDG-PET imaging of atherosclerosis to detect patients at risk of stroke is also feasible and can help test the efficacy of novel anti-atherosclerosis therapies.[18]

Infectious diseases

Imaging infections with molecular imaging technologies can improve diagnosis and treatment follow-up. PET has been widely used to image bacterial infections clinically by using fluorodeoxyglucose (FDG) to identify the infection-associated inflammatory response.

Three different PET contrast agents have been developed to image bacterial infections in vivo: [18F]maltose,[19] [18F]maltohexaose and [18F]2-fluorodeoxysorbitol (FDS).[20] FDS has also the added benefit of being able to target only Enterobacteriaceae.

Pharmacokinetics

Pharmacokinetics: In pre-clinical trials, it is possible to radiolabel a new drug and inject it into animals. Such scans are referred to as biodistribution studies. The uptake of the drug, the tissues in which it concentrates, and its eventual elimination, can be monitored far more quickly and cost effectively than the older technique of killing and dissecting the animals to discover the same information. Much more commonly, drug occupancy at a purported site of action can be inferred indirectly by competition studies between unlabeled drug and radiolabeled compounds known apriori to bind with specificity to the site. A single radioligand can be used this way to test many potential drug candidates for the same target. A related technique involves scanning with radioligands that compete with an endogenous (naturally occurring) substance at a given receptor to demonstrate that a drug causes the release of the natural substance. [21]

Small animal imaging

PET technology for small animal imaging: A miniature PE tomograph has been constructed that is small enough for a fully conscious and mobile rat to wear on its head while walking around.[22] This RatCAP (Rat Conscious Animal PET) allows animals to be scanned without the confounding effects of anesthesia. PET scanners designed specifically for imaging rodents, often referred to as microPET, as well as scanners for small primates, are marketed for academic and pharmaceutical research. The scanners are apparently based on microminiature scintillators and amplified avalanche photodiodes (APDs) through a new system recently invented uses single chip silicon photomultipliers.[citation needed]

In 2018 the UC Davis School of Veterinary Medicine became the first veterinary center to employ a small clinical PET-scanner as a pet-PET scan, for clinical (rather than research) animal diagnosis. Because of cost as well as the marginal utility of detecting cancer metastases in companion animals (the primary use of this modality), veterinary PET scanning is expected to be rarely available in the immediate future.[23]

Musculo-skeletal imaging

Musculoskeletal imaging: PET has been shown to be a feasible technique for studying skeletal muscles during exercises like walking.[24] One of the main advantages of using PET is that it can also provide muscle activation data about deeper lying muscles such as the vastus intermedialis and the gluteus minimus, as compared to other muscle studying techniques like electromyography, which can be used only on superficial muscles (i.e., directly under the skin). A clear disadvantage is that PET provides no timing information about muscle activation because it has to be measured after the exercise is completed. This is due to the time it takes for FDG to accumulate in the activated muscles.

Other Languages
Bahasa Indonesia: Tomografi emisi positron
íslenska: PET-skanni
српски / srpski: Pozitronska emisiona tomografija
srpskohrvatski / српскохрватски: Pozitronska emisiona tomografija