P/F Project 4: Development of CB2R-targeted theranostic PET agent for brain cancer research” (PI: Mingfeng Bai, PhD, Assistant professor, Department of Radiology, Pitt)

Specific Aims. Dr. Bai is a new investigator and recently received his R21 award (R21CA174541, 2013-2016) “A novel theranostic platform for targeted cancer therapy and treatment monitoring”. The objective of his R21 grant is to design a quaterrylene-based dendrimer for targeted cancer therapy and efficacy monitoring. The Bai lab has developed the first quaterrylene-based (QR) near-infrared (NIR) fluorescent theranostic dendrimer platform. With the established technologies in his lab, he also developed a functional CB2R ligand based on a CB2R antagonist, SR144528, which exhibits nanomolar affinity and high binding specificity at CB2R. Research showed that cancers generally over-express CB2R, and the expression levels of CB2R appear to be associated with tumor aggressiveness. Such up-regulation of the receptor in cancer cells provides opportunities in CB2R targeted imaging with high contrast and therapy with low side effects. Therapeutic effects of the CB2 agonist JWH-133 and analogues have been extensively studied in many types of cancers, such as breast, prostate, lung, skin, thyroid and brain cancers. As such, he proposes to develop the first CB2R targeted positron emission tomography (PET) theranostic agent, based on reported/new designed CB2R agonists. The project will benefit from the support of core A and core B. We will focus in computational support for the compound design and ligand-receptor interactions modeling, as such compounds can also have the potential for drug abuse research. In the present P/F project, we proposed two specific aims:Untitled

Aim 1: Computational design and characterize a CB2R targeted theranostic agent

Aim 2: Synthesize and in vitro/in vivo imaging studies of the CB2R theranostic agonist