Radioimmunotherapy (RIT) uses an antibody labeled with a radionuclide to deliver cytotoxic radiation to target cells. Antibody-metal chelating polymers (MCPs) can significantly increase the specific activity of radioimmunoconjugates (RICs). We have developed several types of functional MCPs in which metal chelators on the pendant groups carry radioisotopes suitable for both imaging and therapy, and the end group is available for bioconjugation to antibodies or other targeting moieties. In our first experiments, we used MCPs carrying diethylenetriaminepentaacetic acid (DTPA) to chelate 111In, an Auger emitting radionuclide which also emits two gamma-rays that are useful for microSPECT imaging, and conjugated the MCP to trastuzumab (tmab, Herceptin). Tmab is widely used for breast cancer treatment due to its specific targeting ability towards human epidermal growth factor receptor-2 (HER2), which is overexpressed on some types of breast cancer cells. Recently we turned out attention to pancreatic cancer with the idea of developing MCP reagents that carry 64Cu as combined PET imaging and therapeutic agents. We employed 64Cu-labeled panitumumab F(ab')2 fragments (PmabFab2) that target human epidermal growth factor receptor (EGFR), overexpressed on &gt;90% of pancreatic cancer cells. In order to amplify the sensitivity for imaging and potency for cancer treatment, we examined MCPs with ~20 repeat units, pendant PEG2K chains to provide stealth, and DOTA chelators to bind 64Cu. These polymers were conjugated to lysine amino groups on PmabFab2 via a hydrazone linkage. Orthotopic PC xenografts were visualized by PET/CT imaging. These RICs showed low levels of liver and spleen uptake along with even lower levels of kidney uptake. These encouraging results confirm the stealth properties of the MCPs with pendant PEG2K chains.

Polymer-based radioimmunoconjugates for tumor imaging and cancer therapy

252nd National Meeting (2016)

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