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Technology

This technology is a nitroxide-based brush-arm star polymer organic radial contrast agent (BASP-ORCA). Nitroxide ORCAs have previously been suggested to have potential as a contrast agent. However, nitroxide ORCAs in monomer form are very rapidly reduced to non-functional derivatives in vivo, and they suffer from low proton relaxivity as they possess only one unpaired electron. BASP-ORCAs are polymeric macromolecules that consist of a polyacetal core, many polyethylene glycol (PEG) arms extending from the central core, and a nitroxide group attached at the interface between the core and the PEG arms creating a dense nitroxide layer. This design both protects the nitroxide groups from reduction, and overcomes the low relaxivity of nitroxide monomers by including many nitroxide units, thereby increasing the number of unpaired electrons. Nanoparticles between 10nm and 200nm have been previously demonstrated to accumulate in tumors. BASP-ORCA particles are of an ideal size for tumor accumulation, and indeed BASP-ORCA particles build up in tumors in in vivo mouse tumor transplant models (both subcutaneous and orthotopic models). BASP-ORCA injected intravenously into mice additionally displays clinically relevant circulation half-life, has very low toxicity, and provides negative-contrast enhancement on par with metal-based contrast agents. Finally, other imaging agents and/or drug molecules can be concurrently incorporated into the BASP-ORCA alongside of nitroxides, which provides an additional imaging modality such as IR fluorescence imaging of tumors or combined imaging and therapy strategies.