Preparation and biological evaluation of 111 In-triphenylphosphonium cations / 中华核医学与分子影像杂志

ABSTRACT

Objective To synthesize 4 kinds of 111 In?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 111 In;their lipid?water partition coefficients and in vivo and in vitro stability were evaluated. The binding affinities of 4 kinds of 111 In?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 biologi?cal properties of 4 kinds of 111 In?radiotracers. One?way analysis of variance was used. Results The labeling yields of 4 kinds of 111 In?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.