Metabolotheranostics of metabolites identified by 1H MRS achieved by targeting major metabolic transporters with photoimmunotherapy

Motivation: Many cancers including pancreatic ductal adenocarcinoma (PDAC) lack extracellular antigens or receptors that are cancer-cell specific, presenting a major barrier in their successful treatment. Goal(s): We aim to find new targets for photoimmunotherapy (PIT) of PDAC. Approach: 1H magnetic resonance spectroscopy was used to identify the dysregulated choline, glutamine, and glucose metabolism in PDAC, which helped to exploit the extracellular domain of choline, glutamine, and glucose transporters for PIT using antibody-IR700 conjugates. Results: Our data demonstrate the ability of metabolic transporter-targeted PIT to damage PDAC cells in an expression-dependent manner, providing a path to a metabolotheranostic approach. Impact: Since choline, glutamine, and glucose are dysregulated in most cancers, our studies can significantly expand the scope of targeted cancer treatments that do not express cell surface targets for antibody-drug conjugates or radiotheranostics for systemic therapies.