Toxicities of 166Holmium-chitosan in mice

Abstract

166Holmium (166Ho) is a radionuclide of rare earth chemical and is known to have antitumor activity. Several chemicals were complexed with 166Ho to facilitate the transport of this radionuclide to the site of action. In this study, 166Ho was complexed to chitosan (Chit) which decreases the distribution of Ho into other tissues when applied intrahepatically. To investigate the single dose toxicity, mice were administered intravenously with 1 mCi/kg body weight of 166Ho-Chit (DW-166HC), Chit or nothing. Organ weights, hematological and histopathological studies were performed in 6 animals per group at 1, 3 and 14 days after administration. In 166Ho-Chit treated animals, a slight decrease of erythrocyte number was observed at day 14 and increases of relative liver and lung weights were found at day 3. Although marked multiple necrotic foci in the white pulp and depletion of marginal zone in the spleen were noted at day 1, these findings were decreased in severity and fully recovered at day 3 and day 14, respectively. Slightly decreased kidney weights were observed both in Chit and in 166Ho-Chit treated groups without histological alterations. Thus it is suggested that most effects of 166Ho-Chit observed at an early stage after administration are limited to rapidly dividing cells and reversible within 14 days.