Breast lesions appear as dark spots in the original scan (above, left). Eighteen months later, following treatment, no evidence of breast cancer remains (above, right). Note: The darkened sections in the lower body correspond with natural digestive processes.

PET enables the clinician to view and assess the human body from a functional, biochemical perspective. It compares normal and abnormal tissues at a metabolic rather than morphologic level. As such it is a powerful tool that in various clinical cases can provide a neurologic diagnosis, assess cardiac function, evaluate treatment response, detect tumor recurrence and assist in the grading of certain malignancies.

As a highly sensitive and accurate nuclear medicine imaging technology based on molecular biology, PET has the unique ability to assess the functional and biochemical processes of the body's tissues, which are altered in the earliest stages of virtually all diseases. PET detects these changes—often before anatomical or structural changes have occurred or are evident on MR or CT.

About PET/CT
Literally the combination of PET and CT imaging techniques within a single machine, PET/CT offers the dual benefits of PET’s metabolic information with the anatomical precision of CT. Taking the two scans virtually simultaneously ensures that the patient remains in place and, therefore, that the two images form a precise computer overlay. This fused image provides a more reliable alternative to the traditional side-by-side visual comparison of PET and CT images.

According to a study from Germany, presented at the 2003 meeting of the Radiological Society of North America (RSNA), PET/CT fusion images made a critical diagnostic difference in approximately 20% of cases. PET/CT also eliminates the common problem of a delay between the two studies, during which time the patient's condition may change. In addition to these diagnostic benefits, PET/CT may help radiation oncologists to better tailor radiation fields and aid surgeons in pinpointing biopsy or excision sites.

Images courtesy of Siemens.

The CT image (above left) shows a mass in the right lung. The combined PET/CT image (above right) reveals the metabolic activity of that mass, as well as its precise location in the lung..

PET/CT fusion imaging is most valuable for lung cancer and cancers located in regions of the body that have a complicated anatomy, such as the neck and lower pelvis. Similarly, PET/CT can aid in multifocal diseases, such as lymphoma, by providing more exact locations for biopsies and surgery.

Technical Aspects of PET
PET is an imaging modality that can provide functional, metabolic, and chemical information to complement the more conventional, structural imaging studies. PET essentially records the concentration of positron emitting radioisotopes in a 3-D volume by obtaining external measurements of the radiation emitted by these isotopes. The data is generally acquired as a scaled image of a cross-section of the object to be studied (i.e. transaxially). The intensity of each picture element or picture unit (pixel) is proportional to the isotope concentration at that position in the object.

The most commonly used positron emitting radionuclides are carbon, nitrogen, oxygen, and fluorine. These radionuclides, which emit positrons, are normal components of human tissue. They may exist individually or they may be coupled with some other compound. PET, therefore, can provide an in-vivo study of naturally existing compounds in the human body.

A positron is a positively charged electron that is emitted from the nucleus of a radionuclide. Once emitted this positron (or anti-electron) travels several millimeters (in human tissue in clinical cases) until it meets a free electron from the surroundings and a so-called mutual annihilation event takes place. The masses of the electron and positron are converted to electromagnetic radiation. Due to conservation of energy and momentum, two "annihilation" photons appear (two gamma rays). The total energy of these two photons will equal the rest mass of the original electron and positron (511 Kev) and they will be emitted in a 180 degree opposite direction to one another.

A ring of detectors surrounds the patient and when two 511 Kev gamma rays are simultaneously recorded by opposing detectors, an annihilation event is known to have taken place on or about a line connecting the centers of the two detectors. PET therefore uses the principle of annihilation coincidence detection. Gamma rays from annihilations occurring outside the volume/line that lies between two opposite detectors would only interact with one of these two detectors and not satisfy the coincidence principle. This event then would not be registered.

Physiologic Principles Used in PET
FDG or fluoro-2-deoxyglucose is one of the most commonly used radionuclides in clinical PET. Two-deoxyglucose is a glucose analogue that is as avidly accrued by tumor cells as is glucose. Labeling this compound with Fluorine-18 allows the clinician to record this glucose accumulation as a function of the positron emitter (to measure positron emission as a reflection of glucose accumulation). Normally, once glucose enters into a cell (via a transporter enzyme) it is phosphorylated by an enzyme called hexokinase and then enters directly into either the glycolytic or glycogenic pathway. On the other hand the compound FDG once intracellular, does undergo the phosphorylation step but is subsequently unable to continue into the usual glucose metabolic pathways and is essentially trapped in the cell as FDG-phosphate. The enzyme glucose-6-phosphatase will dephosphorylate in due time both glucose-6-phosphate and FDG-6-phosphate allowing glucose and/or FDG to escape out of the cell.

Different human tissues will have different amounts of hexokinase and glucose-6-phosphatase present, resulting in different patterns of intracellular FDG accumulation. For example the ratio of the concentration of hexokinase to glucose-6-phosphatase is higher in the brain and heart than in other tissues, so that the FDG accumulation in these tissues is predictably higher than in others.

Over the past 60 years, many studies have shown that tumors tend to have an increased rate of glucose utilization with respect to normal tissue. Several reasons may account for this finding including:

• An increase in the concentration and affinity of the enzyme hexokinase due to the extra energy demands of an actively and abnormally dividing cell population.
• Increased transport of glucose into tumor cells, in part due to an increase in the concentration of the carrier protein.
• An increase in glycolytic enzymes such as pyruvate kinase, phospho-fructokinase, and pyruvate dehydrogenase.
• The dephosphorylation rate in tumor cells may be slower than in normal cells. It then follows that the accumulation of FDG-6- phosphate can be used to assess a tumor’s glycolytic rate, which in turn is proportional to a tumor’s proliferation rate and reflective of a tumor’s aggressiveness and rate of growth.

Although various isotopes have been used in clinical and research positron emission tomography including O-15, C-11methionine, Ffluorodopa, two of the most commonly used compounds are N-14-ammonia, and F-18-FDG. F-18-FDG PET has gained a strong foothold in three main clinical areas: neurology, oncology, and cardiology.

Radionuclides used in PET:

• FDG in Neurology
• O-15 in Neurology/Psychiatry
• FDG in Cardiology
• Rubidium in Cardiology
• Ammonia in Cardiology
• C-11 methionine in Oncology
• F-fluorodopa in Neurology