Synthesis and biological evaluation of dimeric RGD peptide conjugated Cu-64 and glucosamine for tumor imaging

1086 Objectives According to recent reports, the dimeric RGD peptide tracer showed higher receptor-binding affinity and specificity for integrin αvβ3 in vitro and enhanced tumor uptake and retention in vivo as compared with the monomeric RGD peptide[1, 2]. Based on above studies, we designed a noble dimeric cyclic RGD labeled radioactive Cu-64 for an effective tumor imaging, which was prepared with two cyclic RGDfK, bifunctional chelator (BFCA) and glucosamine. Glucosamine was used for the purpose of increasing the blood clearance and reducing the liver uptake[3]. Methods The derivatives of glyco-BFCA-di-c(RGDfK) was prepared as three types of NODAGA, NOTA and DOTA. After labeling Cu-64 with analogues of glyco-BFCA-di-c(RGDfK), they were conducted the serum stability test for 24h, respectively. Imaging studies and Biodistribution were used the nude mouse bearing U87MG glioma cancer cell. The organ uptake (10μCi) in U87MG-bearing mice was calculated as a percentage of the injected dose per gram of organ tissue (%ID/g). PET imaging of each dimeric RGD peptide was obtained at 1h, 2.5h, 4h, and 16h as tumor-bearing mice administered with 230μCi into the tail vein. Results The serum stability test of glyco-BFCA-di-c(RGDfK) derivatives was very stable as radiochemical purity of over 95% by ITLC. Biodistribution results of each derivatives were showed higher tumor uptake after 1h as follows : 3.89 ± 0.56 (glyco-NODAGA-di-c(RGDfK)), 3.99 ± 0.98(glyco-DOTA-di-c(RGDfK)), 3.81 ± 0.58(glyco-NOTA-di-c(RGDfK)). In addition, PET imaging of above derivatives was showed the most high uptake of tumor at 1h in mice bearing tumor and was obtained for 40h. Conclusions We introduced Cu-64 labeled glyco-BFCA-di-c(RGDfK) combines easy accessibility with high serum stability and good imaging properties making it an interesting alternative to the monomeric RGD peptide as PET radiopharmaceutical for tumor imaging. Research Support This research was supported from a National Research Foundation of Korea (NRF) grant funded by the Korean government (MEST) (2012-0006388).