'3+1' mixed-ligand oxotechnetium(V) complexes with affinity for melanoma: Synthesis and evaluation in vitro and in vivo

'3+1' Mixed-ligand [Tc-99m]oxotechnetium complexes with affinity for melanoma were synthesized in a one-pot reaction. Complexation of technetium-99m with a mixture of N-R(3-azapentane-1,5-dithiol) [R = Me, Pr, Bn, Et2N(CH2)(2)] and N-(2-dialkylamino)ethanethiol [alkyl = X = Et, Bu, morpholinyl] using Sn2+ as the reducing agent resulted in the formation of '3+1' mixed-ligand technetium-99m complexes [TcO(SN(R)S)(SNX2)] in high radiochemical yield (60-98%). In vitro uptake studies in B16 murine melanoma cells indicated a moderate tumor-cell accumulation (40%) of compound 1 [R = Me, X = Et] and a higher accumulation (69%) of compound 2 [R = Me, X = Bu] after a 60-min incubation. In vivo evaluation of compounds 1-6 in the C57B16/B16 mouse melanoma model demonstrated tumor localization. Compound 2 displayed the highest accumulation with up to 5% ID/g at 60 min after injection. In vivo, 2 also showed a low blood-pool activity and high melanoma/spleen (4.3) and melanoma/lung (1.9) ratios at 1 h. These results suggest that small technetium-99m complexes could be useful as potential melanoma-imaging agents.