Positron emission tomography

Description

A short-lived radioactive tracer isotope which decays by emitting a positron, chemically combined with a metabolically active molecule, is injected into the living subject (usually into blood circulation). There is a waiting period while the metabolically active molecule (usually a sugar) becomes concentrated in tissues of interest, then the subject is placed in the imaging scanner. The short-lived isotope decays, emitting a positron. After travelling up to a few millimeters the positron annihilates with an electron, producing a pair of gamma ray photons moving in opposite directions. These are detected when they reach a scintillator material in the scanning device, creating a burst of light which is detected by photomultiplier tubes. The technique depends on simultaneous or coincident detection of the pair of photons: photons which do not arrive in pairs (ie, within a few nanoseconds) are ignored. By measuring where the gamma rays end up, their origin in the body can be plotted, allowing the chemical uptake or activity of certain part of the body to be determined. The scanner uses the pair-detection events to map the density of the isotope in the body, in the form of slice images separated by about 5mm. The resulting map shows the tissues in which the molecular probe has become concentrated, and is read by a nuclear medicine physician or radiologist, to interpret the result in terms of the patient's diagnosis and treatment. PET scans are increasingly read alongside CT scans, the combination giving both anatomic and metabolic information (what the structure is, and what it's doing). PET is used heavily in clinical oncology (medical imaging of tumours and the search for metastases) and in human brain and heart research.

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

However, while other imaging scans such as CT and MRI, isolate organic anatomic changes in the body, PET scanners are capable of detecting areas of molecular biology detail (even prior to anatomic change) via the use of radiolabelled molecular probes that have different rates of uptake depending on the type of tissue involved. The 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.

Radionuclides used in PET scanning are typically isotopes with short half lives such as Carbon-11, Nitrogen-13, Oxygen-15, and Fluorine-18 (half-lives of 20 min, 10 min, 2 min, and 110 min respectively). Due to their short half lives, the isotopes must be produced in a cyclotron at or near the site of the PET scanner. Currently, 18-F is the only isotope approved by the FDA for distribution in the US. 82-Rb is allowed limited use for myocardial perfusion experiments. These isotopes are incorporated into compounds normally used by the body such as glucose, water or ammonia and then injected into the body to trace where they become distributed.

PET as a technique for scientific investigation is limited by the need for clearance by ethics committees to inject radioactive material into participants, and also by the fact that it is not advisable to subject any one participant to too many scans. Furthermore, due to the high costs of cyclotrons needed to produce the short-lived radioisotopes for PET scanning (for example 18-F), few hospitals and universities are capable of performing PET scans.

However, with the recent decision of Medicare to cover PET scans for specific patients, there has been a recent trend of increase in clinical use of PET scans throughout the United States. [1]

Applications

PET is a valuable technique for some diseases and disorders, because it is possible to target the radio-chemicals used for particular bodily functions.

1. Oncology: PET scanning with the tracer (¹⁸F) fluorodeoxyglucose (FDG, FDG-PET) is widely used in clinical oncology. This tracer mimics glucose and is taken up and retained by tissues with high metabolic activity, such as the brain, the liver, and most types of malignant tumour. As a result FDG-PET can be used for diagnosis, staging, and monitoring treatment of cancers. However because individual scans are more expensive than conventional imaging with CT and MRI, expansion of FDG-PET in cost-constrained health services will depend on proper Health Technology Assessment. Oncology scans using FDG make up over 90% of all PET scans in current practice.
2. Neurology: PET brain imaging 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 generally believed to be correlated, and usually measured using the tracer oxygen (¹⁵O). Research continues into the use of radiolabelled F-DOPA and FDDNP as more specific probes.
3. Cardiology: In clinical cardiology FDG-PET can identify so-called "hibernating myocardium", but its cost-effectiveness in this role versus SPECT is unclear.
4. Neuropsychology / Cognitive neuroscience: To examine links between specific psychological processes or disorders and brain activity.
5. Pharmacology: In pre-clinical trials, it is possible to radio-label a new drug and inject it into animals. 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. PET scanners for rats and apes are marketed for this purpose.
   

   PET scans safety

Because the half-life of 18F is about two hours, the prepared doses decay significantly during the working day. If the FDG is delivered to the scanning suite in the morning, the specific activity falls during the day, and a relatively larger volume of radiopharmaceutical must be injected in later patients to deliver the same radioactive dose.

The radioactive dose to the patient is small, however the dose to the operators is a limiting factor in the operation of a PET facility.

PET history and current deployment

Edward J. Hoffman and Michael Phelps developed the first human PET scanner in 1973 at Washington University in St. Louis. See also history of brain imaging.

PET scanning is a capital-intensive and very specialised technique which is limited to facilities close to a cyclotron for 18-F FDG, and in the same building as the cyclotron for shorter halflife isotopes. Although developed in the 1970s, PET scanning was limited to research until the US Medicare system announced reimbursement for certain specific conditions, such as the staging of particular cancers. Oncology reimbursement now drives the majority of PET installations, which are concentrated in major US cities and particularly in the retirement states such as Florida. Insurance reimbursement for a PET scan is typically in the area of $1500 which is divided between the operator of the scanner and the interpreting physician.

The most significant industry trend in PET today is the combination of PET and CT scanners into a single unit, providing registered images of the patient in both modalities. This is a significant aid in the interpretation of PET data, since anatomical structures are not clear in the PET image. However, although a CT scan is taken in just a few seconds (minimizing the effects of patient movement, breathing, heartbeat and bowel action), the PET scan takes around half an hour, so the registration of the two is not precise.

See also