Neutron activation of In(III) complexes with thiosemicarbazones leads to the production of potential radiopharmaceuticals for the treatment of breast cancer

In(III) complexes [In(2Ac4oClPh)(2)]NO3 (1) and [In(2Ac4pFPh)(2)]NO3 center dot 1.5H(2)O (2) were obtained with N(4)-ortho-chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4oClPh) and N(4)-para-fluorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4pFPh). Neutron activation of complexes (1) and (2), and of previously prepared [In(2Ac4oClPh)Cl2(MeOH)] (3) and [In(2Ac4pFPh)Cl-2(MeOH)] (4) resulted in the formation of (114)mIn/(115)mIn analogues (*1*4). The cytotoxic activities of the compounds under study were investigated on MCF-7 breast cancer cells as well as against non-malignant MRC-5 fibroblast cells. Upon coordination to In(III) the cytotoxicity against MCF-7 cells significantly increased in complexes (14), suggesting that complexation was a good strategy to improve the cytotoxic effect. While both non-radioactive and radioactive In(III) salts were inactive against MCF-7 cells, the radioactive complexes (*1*4) proved to be 102 to 104 times more potent than the non-radioactive analogues (14). For the non-radioactive In(III) complexes (14) the selectivity indexes (SI), defined as IC50MRC-5/IC50MCF-7, were SI = 0.070.36, while high values of SI were found for the radioactive In(III) analogues (*1*4), SI = 464716, indicating that irradiation represented an interesting strategy for increasing the selectivity. Since cytotoxicity was evaluated following 48 h of treatment and 72 h after neutron activation, the observed cytotoxic effects were attributed mainly to (114)mIn, the contribution of the (115)mIn (t1/2 = 4.5 h) isomer being considered irrelevant. Complexes (*1*4) induced higher levels of intracellular ROS in MCF-7 cells in comparison to the parent compounds. The results suggest that (114)mIn complexes with thiosemicarbazones might show potential for application as radiopharmaceuticals for the treatment of breast cancer.