Synthesis and biological evaluation of silylated mixed-ligand 99mTc complexes with the [PNS/S] donor atom set

Abstract

New oxotechnetium complexes of general formula [ 99mTc(O)(PNS)(S(CH 2) n OSiR 3)] ( 4– 6) were synthesized by direct reduction of [ 99mTcO 4] − with stannous chloride, in the presence of the tridentate heterofunctionalized phosphine H 2PNS and of the monodentate silylated thiols [HS(CH 2) n OSiR 3] ( n=2, R=Ph ( 1); n=3, R=Ph ( 2); n=3, R=Et ( 3)). The mixed-ligand rhenium and technetium complexes of general formula [M(O)(PNS)(S(CH 2) n OH)] ( n=2: M= 99mTc, ( 7), M=Re, ( 7a); n=3: M= 99mTc, ( 8), M=Re, ( 8a)) were also prepared. All the 99mTc complexes were obtained with high radiochemical purity (>95%), after purification by HPLC, and were characterized by comparison of their HPLC profiles with the ones obtained for the corresponding Re compounds. The silylated compounds 4– 6 are stable in phosphate saline buffer (PBS) pH 7.4, rat plasma, human serum and whole blood, and do not bind to plasmatic proteins, and also do not challenge with glutathione. The biological behavior of [ 99mTc(O)(PNS)(S(CH 2) n OH)] ( 7, 8) and [ 99mTc(O)(PNS)(S(CH 2) n OSiR 3)] ( 4– 6) was studied. The effect of the pH on the cleavage of the O-Si bond in complexes 4– 6 was also evaluated.