Stability and Biodistribution of Thiol-Functionalized and 177Lu-Labeled Metal Chelating Polymers Bound to Gold Nanoparticles
2016
We are studying a novel radiation nanomedicine approach to treatment of breast cancer using 30 nm gold nanoparticles (AuNP) modified with polyethylene glycol (PEG) metal-chelating polymers (MCP) that incorporate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators for complexing the β-particle emitter, 177Lu. Our objective was to compare the stability of AuNP conjugated to MCP via a single thiol [DOTA-PEG-ortho-pyridyl disulfide (OPSS)], a dithiol [DOTA-PEG-lipoic acid (LA)] or multithiol end-group [PEG-pGlu(DOTA)8-LA4] and determine the elimination and biodistribution of these 177Lu-labeled MCP-AuNP in mice. Stability to aggregation in the presence of thiol-containing dithiothreitol (DTT), l-cysteine or glutathione was assessed and dissociation of 177Lu-MCP from AuNP in human plasma measured. Elimination of radioactivity from the body of athymic mice and excretion into the urine and feces was measured up to 168 h post-intravenous (i.v.) injection of 177Lu-MCP-AuNP and normal tissue u...
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