Preparation and biological evaluation of 111In-triphenylphosphonium cations

Abstract

Objective To synthesize 4 kinds of 111In-TPP cations and evaluate their properties as tumor cationic radiotracers in vivo and in vitro. Methods DO3A-xy-TPP, DO3A-xy-mTPP, DO3A-xy-dmTPP and DO3A-xy-tmTPP were radiolabeled with 111In; their lipid-water partition coefficients and in vivo and in vitro stability were evaluated. The binding affinities of 4 kinds of 111In-radiotracers were determined in cell uptake and cell efflux assay using U87MG tumor cells. Biodistribution studies and γ imaging studies were performed using the athymic nude mice bearing U87MG human glioma xenografts to explore the biological properties of 4 kinds of 111In-radiotracers. One-way analysis of variance was used. Results The labeling yields of 4 kinds of 111In-radiotracers were all above 85%, and the radiochemical purity were all greater than 99% after purification. Binding assay in U87MG cells showed that 4 kinds of radiotracers had great binding affinity and cell retention ability, and 111In-DO3A-xy-mTPP had the best binding ratio (1.49%; F=177.8, P<0.05). Gamma imaging and biodistribution results showed that the U87MG tumors could be clearly visualized by 111In-DO3A-xy-mTPP, 111In-DO3A-xy-dmTPP and 111In-DO3A-xy-tmTPP, and the liver uptake of the 3 tracers was lower than that of 111In-DO3A-xy-TPP. In particular, 111In-DO3A-xy-mTPP had the best tumor/liver ratio (0.13±0.05, 2 h postinjection; F=9.4, P<0.05). Conclusions The tumor-targeted ability of 111In-DO3A-xy-mTPP is better than those of 111In-DO3A-xy-dmTPP, 111In-DO3A-xy-tmTPP and 111In-DO3A-xy-TPP, suggesting that it has the potential to be a promising tumor cationic radiotracer. Key words: Triphenylphosphonium; Isotope labeling; Indium radioisotopes; Glioma; Radionuclide imaging; Mice, nude