Comparison of BTSE-RGD with DOTA-RGD as a potential imaging agent for tumors

RGD and its analogues are very important compounds and can be used as potential tumor-targeting agents. Bisthiosemicarbazone-conjugated RGD (BTSE-RGD) and DOTA-RGD were prepared using a chemical strategy based on peptide synthesis and chemoselective ligations. BTSE-RGD comprises two domains, the first a tumour selective domain and the other a chelating vehicle, for conjugation of radioisotopes. Both compounds were synthesized and labelled with Tc-99m and radiochemically analysed by HPLC. The stability of the radioconjugate in the presence of human serum was checked at 37 degrees C up to 8 h. Labelling yield of 96.8 +/- 0.32% was obtained, which corresponds to a specific activity in the range of 36-89 MBq mu mol(-1) for BTSE-RGD. The BTSE-RGD conjugate was examined in vitro for its ability to bind with the alpha(v)beta(3) receptor. The functionalized BTSE-RGD displayed a binding affinity toward alpha(v)beta(3) integrin (31.9 +/- 6.8 nM) many-fold better than DOTA-RGD. Tc-99m-BTSE-RGD showed a slower distribution half-life (T-1/2 beta) and elimination half-life (T-1/2 beta) of 65 +/- 0.001 min and 21 h 15 min + 0.001 min, respectively, in comparison to Tc-99m-DOTA-RGD, with T-1/2 alpha of 18 +/- 0.001 min and T-1/2 beta of 9 h 10min +/- 0.005 min. Biodistribution study showed better tumor-to-muscle ratio for BTSE-RGD, which reaches maximum around 3.5 (% ID) in 2 h, while for DOTA-RGD the maximum was 13.60 at 24 h.