TOXICITIES OF (166)HOLMIUM-CHITOSAN IN MICE

(166)Holmium (Ho-166) is a radionuclide of rare earth chemical and is known to have antitumor activity. Several chemicals were complexed wit h Ho-166 to facilitate the transport of this radionuclide to the site of action. In this study, Ho-166, was complexed to chitosan (Chit) whi ch decreases the distribution of Ho into other tissues when applied in trahepatically. To investigate the single dose toxicity, mice were adm inistered intravenously with 1 mCi/kg body weight of Ho-166-Chit (DW-1 66HC), Chit or nothing. Organ weights, hematological and histopatholog ical studies were performed in 6 animals per group at 1, 3 and 14 days after administration. In Ho-166-Chit treated animals, a slight decrea se of erythrocyte number was observed at day 14 and increases of relat ive liver and lung weights were found at day 3. Although marked multip le necrotic foci in the white pulp and depletion of marginal zone in t he spleen were noted at day 1, these findings were decreased in severi ty and fully recovered at day 3 and day 14, respectively. Slightly dec reased kidney weights were observed both in Chit and in Ho-166-Chit tr eated groups without histological alterations. Thus it is suggested th at most effects of Ho-166-Chit observed at an early stage after admini stration are limited to rapidly dividing cells and reversible within 1 4 days.