Cancer is a dynamic and heterogeneous disease that requires techniques able to assess biological processes in the entire tumor tissue and in real time. One non-invasive imaging technique with high potential for clinical translation is immunoPET. ImmunoPET combines positron-emitting radioisotopes with an antibody's ability to bind to a target expressed in high levels in the tumor cells. Dr. Lewis, Glenn T. Seaborg Awardee, is a leader in the field of immunoPET, and it was under his mentorship that I learned how to use this technique to understand biological processes of tumor resistance. This is now a major research area in my laboratory, and in this talk honoring Dr. Lewis, I will share two major lessons learned in the last few years: 1. Membrane target availability affects immunoPET and tumor response to antibody therapy. Receptors are not always available at the cell membrane of cancer cells for antibody binding because they can be internalized through endocytosis. We have developed pharmacologic approaches that modulate these processes in ways that enhance therapeutic efficacy. More specifically, we demonstrated that cholesterol-depleting drugs (statins) enhance membrane receptor availability and improve antibody efficacy. Our preclinical findings provided justification for ongoing clinical investigations of antibody drugs combined with statins. 2. Endocytic processes can be modulated to allow for pretargeted therapy of internalizing membrane receptors. Antibodies bearing long-lived therapeutic radioisotopes present an unwanted clinical complication: unnecessarily high radiation dose rates to healthy tissues. Pretargeted approaches—the antibody and a radiolabeled small molecule administered separately combine within the body—offer a potential alternative to the use of radiolabeled antibodies. However, this methodology depends on the presence of the target at the cell membrane. In exploring the role of endocytosis in receptor stability at the cell membrane, we pharmacologically anchored receptors on the cell surface to outperform previous attempts of pretargeting internalizing receptors.

Imaging tumor biology: Lessons learned in the Lewis Lab

Where thousands of chemistry professionals meet to share ideas and advance scientific and technical knowledge. Spring 2023 abstracts, posters, and presentations will launch at the end of March.

ACS Spring 2023

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.