Synthesis of FASN-Specific Novel PET Tracers for Improved Prostate Cancer Diagnosis

Prostate cancer is projected to account for nearly 29% of all cancer diagnoses in the U.S. in 2023, with an estimated 288,300 new cases and 34,700 fatalities, underscoring its position as leading cancer among men. While strides have been made in early detection, the prevalent risk assessment methods, including clinical T-stage, PSA count, and the Gleason score, often fall short in distinguishing between the disease's indolent and aggressive form. Consequently, there is a growing demand for innovative biomarkers to refine prognosis assessments and therapeutic monitoring by accurately characterizing cancer phenotypes. A promising candidate is the lipogenic enzyme, Fatty acid synthase (FASN; E.C.2.3.1.85), due to its central role in the lipogenesis and tumor cell proliferation (Warburg effect), along with its varied expression levels between tumors and normal tissue. The potential to image its activity using radiolabeled molecules opens new doors for tumor assessment and therapeutic strategy formulation. Positron emission tomography (PET) stands out as a significant, non-invasive technique to visualize cancer traits in vivo. This dissertation centers on: (1) a comprehensive review of early-stage prostate cancer diagnosis, and (2) crafting PET tracers for in vivo FASN imaging, with the goal of advancing the predictive and pharmacodynamic understanding of prostate cancer. Inspired by two potent classes of FASN inhibitors, GSK-class and TVB-class, several new probes were synthesized, and their biological performance evaluated.