Preparation of 68Ga-DOTA-cRGD and its utility for lung adenocarcinoma bearing nude mice imaging

Objective To synthesize 68Ga-DOTA-cyclic RDG (cRGD), to evaluate its biodistribution in nomal mice, and to perform 68Ga-DOTA-cRGD microPET imaging on nude mice bearing lung adenocarcinoma (LA) xenografts. Methods 68Ga-DOTA-cRGD was synthesized in HEPES buffer system (pH 5.0). The radiolabeled yield and radiochemistry purity were measured with HPLC. The biodistribution in the normal mice was investigated. 68Ga-DOTA-cRGD was injected into nude mice bearing A549 LA via tail vein. Dynamic and static images were acquired using microPET. ROI was drawn to calculate the T/NT ratio. The expression of αvβ3 in LA xenografts was observed by immunohistochemistry and flow cytometry. Results The radiolabeling yield was (97.8±0.1)% and the radiochemical purity was 95% after 2 h. The biodistribution in normal mice showed rapid clearance from blood, the blood uptakes of 68Ga-DOTA-cRGD were (1.65±0.85) %ID/g and (0.06±0.02) %ID/g at 5 and 120 min postinjection. 68Ga-DOTA-cRGD was excreted mainly via kidney, and little radioactivity were accumulated in the liver and gastrointestinal tract. Marked uptake of 68Ga-DOTA-cRGD was found in tumor tissue of the nude mice bearing LA with maximum T/NT ratio of 5.93±0.43 at 60 min postinjection. The expression of αvβ3 was observed on LA xenograft tissues. Conclusions 68Ga-DOTA-cRGD can be easily prepared with high radiolabeling yield and radiochemical purity. The good stability and biodistribution characteristics make it useful for the diagnosis of human lung cancer with over expressed αvβ3 receptor. Key words: Peptides, cyclic; Arg-Gly-Asp; DOTA; Isotope labeling; Gallium radioisotopes; Lung neoplasms; Mice