Zhengxin (Jason) Cai, PhD, Assistant Professor, Yale University PET Center, has been awarded an R03 grant from the National Institutes of Health (NIH) to develop a PARP PET radiotracer. Tumor cells can survive chemo/radiation therapies through DNA repairment mediated by poly(ADP-ribose) polymerase-1 (PARP-1). However, PARP-1 inhibitors (PARPis) used alone, or in combination with chemotherapy or radiation therapy, obstruct single strand DNA repair and have led to substantial gains in the overall survival of cancer patients. Multiple ongoing clinical trials are using PARPis to treat glioma and to assess baseline PARP expression levels through quantitative PARP PET imaging, thereby providing prognostic information. None of the current PARP imaging agents under development is brain penetrant, making the reliable quantification of PARP-1 in brain challenging. With this study, we propose to evaluate a brain penetrant PARP-1 inhibitor and its analogs as potential PET imaging agents. Collaborators on this project include Drs. Henk De Feyter, Mark Saltzman, and Ranjit Bindra.
Submitted by Angel Machon on April 27, 2020