Developing a MALDI/PET Early Warning Imaging System for Lethal Prostate Cancer
Abstract
Prostate cancer is not only heterogeneous among individuals, but tumors are heterogeneous on the molecular level within a given individual. One well-documented phenomenon is the presence of castrate-resistant prostate cancer with neuroendocrine features (CRPC-NE) that evolves over the course of anti-androgen therapy. Our group has discovered that CRPC-NE have a unique cell surface glycan composition enriched with fucose sugars. Therefore, the ability to image glycan fucosylation could be used to predict the emergence of lethal prostate cancer in men. This proposal tests the feasibility of a previously developed PET agent, [18F] fluorofucose (Fuc-PET) as a functional method to quantify PCa glycan fucosylation, and thus, the burden of lethal disease using animal models. Our hypothesis is that Fuc-PET can quantify the amount of glycan fucosylation in tumors noninvasively and thus predict aggressive pathology in vivo. In the first year, we have made advancements in the characterization of fucose modifications to glycans through core glycan modifications and the synthesis of the Lewis-y antigen that are associated with more aggressive disease and shorter survival. We have also discovered that the ketogenic diet can inhibit the synthesis of these fucosylated glycans, suggesting that dietary modifications could enhance therapeutic efficacy in men with advanced prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2020
- Accession Number
- AD1125475
Entities
People
- Joseph Ippolito
Organizations
- Medical University of South Carolina
- Northwestern University
- Washington University in St. Louis