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 99mTc and radiochemically analysed by HPLC. The stability of the radioconjugate in the presence of human serum was checked at 37 °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 μmol−1 for BTSE-RGD. The BTSE-RGD conjugate was examined in vitro for its ability to bind with the αvβ3 receptor. The functionalized BTSE-RGD displayed a binding affinity toward αvβ3 integrin (31.9 ± 6.8 nM) many-fold better than DOTA-RGD. 99mTc-BTSE-RGD showed a slower distribution half-life (T1/2α) and elimination half-life (T1/2β) of 65 ± 0.001 min and 21 h 15 min ± 0.001 min, respectively, in comparison to 99mTc-DOTA-RGD, with T1/2α of 18 ± 0.001 min and T1/2β of 9 h 10 min ± 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.