Positron emission tomography, or PET, is a medical imaging technique that employs trace amounts of short-lived species of carbon, fluorine, nitrogen, oxygen, and metal ions that decay by the emission of a positron, the anti-particle of the electron. These species of unstable atoms do not occur naturally, but rather must be produced in a nuclear reactor or on-site using a type of particle accelerator called a cyclotron. The cyclotron uses strong electric fields to accelerate charged particles (e.g., a proton) to high energies and it uses strong magnetic fields to contain and direct the accelerated particles.
At a terminal point in an expanding circular pathway, they are redirected to bombard fixed targets where nuclear reactions occur that yield the desired positron-emitting radionuclides. The positron, which is emitted from the decaying nucleus with a characteristic kinetic energy spectrum, loses nearly all of its kinetic energy through successive electrostatic interactions with other atoms in its surroundings, after which point it forms a bound state with a free electron called positronium. This bound state of matter (electron) and anti-matter (positron) is extremely short-lived (less than one-billionth of a second!), at which time the electron and positron mutually annihilate. During the process of annihilation, the rest masses of the two particles are converted into electromagnetic radiation in the form of a pair of gamma rays, each with a characteristic energy of 511 thousand electron volts (keV). The gamma rays are emitted in opposite directions along a line, which is the basis for their detection using specialized instruments called PET scanners, which record large numbers of these types of events in the field of view of the instrument and map out their distribution in space and time.
By labeling molecules of biological significance with these short-lived positron-emitting radionuclides and mapping out their distribution within the body, it is possible to use PET to study biological processes in living people in a non-invasive manner. Using these techniques, important information regarding the function of organs and tissues can be made without the use of surgical incisions, biopsy needles, etc. For instance, a radiolabeled analog of glucose called FDG is widely used in clinical practice to identify cancerous tissues in the body, based on the fact that many cancerous tissues have higher metabolic energy demands than normal tissue. The FDG radiotracer will preferentially accumulate in the cancerous tissue, appearing as a “hot spot” on the PET scan. By overlaying this functional information with an anatomical image, typically a CT scan, the radiologist can identify the location of the suspected cancer lesion with the greatest confidence. This information is used by oncologists to determine the optimum treatment plan for the patient, as well as to assess the efficacy of the treatment by follow-up PET scans.
In addition to its clinical utility, PET scans are a very valuable research tool as they permit research to be conducted in human subjects with a minimum of discomfort and risk to the subject. For instance, PET can be used to probe various aspects of neurochemical function within the brain that may have relevance to psychiatric conditions as well as diseases of the central nervous system. A PET imaging technique was developed at the University of Pittsburgh for identifying abnormal deposits of the beta-amyloid (Aβ) protein, which is one of the pathological hallmarks of Alzheimer’s disease (AD) and also the substrate that is widely believed to be a key abnormality leading to the clinical syndrome of Alzheimer’s dementia. The high sensitivity of PET allows the detection of relatively small amounts of Aβ in the brain long before the symptoms of the clinical disease are apparent (i.e., before significant memory loss). This is critically important for the development of novel disease modifying therapies targeting Aβ, as well as identifying patients likely to benefit from such therapies. Amyloid imaging is now used throughout the world for investigational studies of dementia. Several commercially available PET amyloid imaging agents have been cleared by the FDA and are beginning to be used clinically to aid in the diagnosis of AD.
The PET Facility at the University of Pittsburgh has been operational since 1992, and is administered as a research division of the Department of Radiology under the direction of Chester A Mathis, Ph.D. The PET Facility is housed in over 12,000 square feet of the 9th floor of the B-wing in Presbyterian-University Hospital, University of Pittsburgh Medical Center (UPMC) Health System. This space includes three scanner bays serviced by two control rooms, inpatient and outpatient preparation rooms, and a small wet laboratory outfitted with an array of radiation detection instrumentation for blood and radiolabeled metabolite assays. The PET Radiochemistry Laboratory is included within the PET Facility and is divided into a cold chemistry laboratory of 1000 sq. ft., a hot radiochemistry laboratory of 1000 sq. ft., and a 1200 sq. ft. cyclotron vault that houses a Siemens Eclipse HP medical cyclotron and ancillary supporting electronics and equipment. Research investigators, students, and PET Facility staff utilize a common data and image processing laboratory that is outfitted with hardware and software for performing PET data analyses. Offices for the PET Facility director, physicists, chemists, computer programmers, research faculty, residents and post-doctoral fellows, nurses, and nuclear medicine technologists are also contained within the facility. Presently, the PET Facility comprises a dedicated full time research staff of approximately 30, including nine full-time Radiology faculty members. The staff also includes nuclear medicine fellows and post-docs, radiochemistry technicians, data analysts, systems administrators, research coordinators, nuclear medicine technologists, and administrative staff. Located on the University of Pittsburgh Main Campus, the PET Facility benefits from its central location to the major clinical and research activities of the institution. The PET Facility maintains an array of dedicated research scanners and equipment. Although the emphasis of the research facilities is on neuroimaging initiatives, a growing component of research in oncology and other systemic disorders continues to diversify its research efforts.