PET: Radiotracer Development

Radiotracer development activities within the PET Facility focus primarily on neuroscience applications, with an emphasis on in vivo imaging of neurodegenerative disease pathology. Since its inception in 1992, Dr. Chester Mathis, Director of the PET Facility and Senior Radiochemist, has led these efforts. A long-standing collaboration with the laboratory of Dr. William E. Klunk, Dept. of Psychiatry, yielded the first successful PET imaging agent for imaging beta-amyloid (Aβ) plaques, an abnormal protein aggregate that is one of the pathologic hallmarks of Alzheimer’s Disease (AD). This agent, [11C]Pittsburgh Compound B (or [11C]PiB), continues to be an important investigational tool used worldwide in human AD research. A radiofluorinated analog of PiB developed by the PET Facility is under license to GE Healthcare, which is marketed as Vizamyl™ and approved by the U.S. FDA for clinical use. Currently, efforts in this area of research are focused on the development and application of PET imaging agents targeting deposits of hyperphosphorylated tau, another abnormal protein aggregate implicated in AD and other neurodegenerative diseases. With the support of the Michael J. Fox Foundation, the PET Facility is working to identify novel compounds that bind with high affinity and selectivity to brain α-synuclein deposits that are characteristic of Parkinson’s disease (PD) and Lewy-body dementia (DLB). The ultimate goal of this research is to identify a compound or a class of compounds that can be labeled with 11C or 18F to image PD pathology in vivo.

In addition to its focus on developing novel PET radiotracers for neurodegenerative disease applications, the PET Facility Radiochemistry Laboratory supports a breadth of human investigational neuroimaging studies by synthesizing over 30 different radiotracers that target specific populations of serotonin receptors and transporters (5HT-2A, 5-HT1A, 5-HTT), dopamine receptors and transporters (D2, DAT), vesicular monoamine transporters (VMAT2), translocator protein 18kDa (TSPO), and the nociception/orphanin FQ peptide (NOP) receptor.

Areas of Research Interest

The majority of human research studies conducted at the University of Pittsburgh PET Facility can be classified as neuroscience related, comprising over 40 active protocols under the direction of more than 20 principal investigators from five different academic departments within the University of Pittsburgh School of Medicine (UPSOM) and the Graduate School of Public Health (GSPH). Areas of research emphasis in clinical neuroscience include studies of dementia, aging, addiction, sleep disorders, alcohol dependence, acquired brain injury, and stroke. Complementing the strong program of neuroscience imaging research is a growing component of oncology and infectious disease research. Several radiotracers with relevance to oncology imaging are supported for human investigational use, which include [18F]FDG (glucose metabolism), [18F]FLT (proliferation index), and [18F]FMISO (hypoxia agent). Preclinical imaging is supported by the PET Facility research tomographs and radiochemistry facilities. The PET Facility supports the University of Pittsburgh Regional Biocontainment Laboratory (RBL), which is one a handful of laboratories worldwide that is equipped to support PET/CT imaging in biosafety level 3 (BSL-3) for highly pathogenic infectious disease research.