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(2Ac4 o ClPh) 2 ]NO 3 ( 1 ) and [In(2Ac4 p FPh) 2 ]NO 3 ·1.5H 2 O ( 2 ) were obtained with N (4)- ortho -chlorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4 o ClPh) and N (4)- para -fluorophenyl-2-acetylpyridine thiosemicarbazone (H2Ac4 p FPh). Neutron activation of complexes ( 1 ) and ( 2 ), and of previously prepared [In(2Ac4 o ClPh)Cl 2 (MeOH)] ( 3 ) and [In(2Ac4 p FPh)Cl 2 (MeOH)] ( 4 ) resulted in the formation of 114m In/ 115m In 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 ( 1–4 ), 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 10 2 to 10 4 times more potent than the non-radioactive analogues ( 1–4 ). For the non-radioactive In( iii ) complexes ( 1–4 ) the selectivity indexes (SI), defined as IC 50 MRC-5 /IC 50 MCF-7 , were SI = 0.07–0.36, while high values of SI were found for the radioactive In( iii ) analogues ( *1–*4 ), SI = 46–4716, 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 114m In, the contribution of the 115m In ( t 1/2 = 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 114m In complexes with thiosemicarbazones might show potential for application as radiopharmaceuticals for the treatment of breast cancer.