Tumor vasculature is commonly characterized as abnormally “leaky”. This characteristic, combined with impaired lymphatic drainage, leads to the accumulation of macromolecular agents in the tumor—a phenomenon termed the Enhanced Permeability and Retention (EPR) effect. While the EPR effect has been extensively investigated to improve chemotherapy, less research has been conducted on utilizing this mechanism for internal radionuclide therapy. By synthesizing polymers with pendant chelating ligands that can bind to radionuclides, the EPR effect can be used to target tumors. A key consideration, however, is understanding the interplay between the polymer structure, radiometal coordination, and in vivo stability. To explore these interrelationships, we synthesized a series of linear polyethyleneimine methylphosphonates with varying molecular weight and degrees of functionalization. We then quantified the thermodynamics of metal chelation with diagnostically or therapeutically relevant lanthanides using isothermal titration calorimetry. Dynamic light scattering experiments were also performed to determine the effect of metal coordination on the hydrodynamic radius of the polymers and on aggregation behavior in solution. These two parameters—size and aggregation—are critical to understanding in vivo biodistribution since the EPR effect is believed to be size dependent. These data will inform future designs of polymeric radiopharmaceuticals with predictable radiometal binding profiles and tunable size distributions.

Polymeric radiopharmaceuticals: Exploring the connection between polymer structure and radiometal chelation

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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