development of an inflammation imaging tracer, 111 in-dota-dapta, targeting chemokine receptor ccr5 and preliminary evaluation in an apoe −/− atherosclerosis mouse model

Chemokine receptor 5 (ccr5) plays an important role in atherosclerosis. our objective was to develop a spect tracer targeting ccr5 for imaging plaque inflammation by radiolabeling d-ala-peptide t-amide (dapta), a ccr5 antagonist, with 111in. 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (dota) conjugated dapta (dota-dapta) was labeled with 111in. cell uptake studies were conducted in u87-cd4-ccr5 and u87-mg cells. biodistribution was determined in c57bl/6 mice. autoradiography, en face and oil red o (oro) imaging studies were performed in apoe−/− mice. dota-dapta was radiolabeled with 111in with high radiochemical purity (> 98%) and specific activity (70 mbq·nmol). 111in-dota-dapta exhibited fast blood and renal clearance and high spleen uptake. the u87-cd4-ccr5 cells had significantly higher uptake in comparison to the u87-mg cells. the cell uptake was reduced by three times with dapta, indicating the receptor specificity of the uptake. autoradiographic images showed significantly higher lesion uptake of 111in-dota-dapta in apoe−/− mice than that in c57bl/6 mice. the tracer uptake in 4 month old apoe−/− high fat diet (hfd) mice with blocking agent was twofold lower than the same mice without the blocking agent, demonstrating the specificity of the tracer for the ccr5 receptor. 111in-dota-dapta, specifically targeting chemokine receptor ccr5, is a potential spect agent for imaging inflammation in atherosclerosis.