Drug Designing: Open Access
Open Access

Abstract

New Potential In Situ Anticancer Agent Derived from [¹⁸⁸Re]rhenium Nitro-Imidazole Ligand Loaded 5th Generation Poly-L-Lysine Dendrimer for Treatment of Transplanted Human Liver Carcinoma in Nude Mice

Guanghua Yang, Nouredine Sadeg and Hafid Belhadj-Tahar

Hepatocellular carcinoma (HCC) is the most common primary liver tumor and one of the fifth most common tumors worldwide. In this article we report the results of in vivo studies of potential anticancer agent "[188Re] rhenium-ImDendrim" derived from [188Re]rhenium-nitro-imidazole-methyl -1,2,3-triazol-methyl-di-(2-pycolyl)amine as radioactive ligand loaded 5th generation poly-L-lysine denrimer (172,3 kDa, 20 nM). Methods: 5.0 × 10⁶ cells were subcutaneously injected into mice. Once tumor established, 4 mice lots were treated with a single dose of the test item (37, 74, 92.5 and 111 MBq of [188Re]rhenium-ImDendrim, respectively) compared to control lots (free [188Re]rhenium and non-radioactive ImDendrim). By the end of the study in six weeks post-test compound administration, the tumors were collected for histological analysis. Results: The treatment was well tolerated. In fact, [188Re]rhenium-ImDendrim shows high significant anti-tumor property in this experimental cancer model even with the lowest dose of 37 MBq compared to control groups. These results were further confirmed by histological analysis. Large tumor mass only observed in tumor's sections from mice in the control groups, were disappeared in favour of collagen tissue in treated groups. In conclusion, this novel potential radiopharmaceutical agent has giving promising experimental results by showing an anti-tumoral activity in this experimental of liver cancer model in mice under the tested conditions.