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

New oxotechnetium compleses of general formula [^99mTc(O)(PNS)(S(CH₂)_nOSiR₃] (4-6) were synthesized by direct reduction of [[^99mTcO₄]^- with stannous chloride, in the presence of the tridentate heterofunctionalized phosphine H₂PNS and of the monodentate silylated thiols [HS(CH₂)_nOSiR₃] (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(CH₂)_nOH] (n=2: M=^99mTc, (7), M=Re, (7a); n=3: M=^99m, (8), M=Re, (8a)) were also prepared. All the ^99mTc complexes were obtained with high radiochemical purity (> 95 %), after purification by HPCL, 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(CH₂)_nOH] (7, 8) and [^99mTc(O)(PNS)(S(CH₂)_nOSiR₃] (4-6) was studied. The effect of the pH on the cleavage of the O-Si bond in complexes 4-6 was also evaluated.