Radiochemical and biological evaluation of novel 153Sm/ 166Ho-amino acid-chitosan complexes

Abstract

153Sm/166Ho-chitosan complexes have been considered promising agents for internal radiation therapy. By direct administration, complexes solution converts into a gel, at physiological pH, allowing its retention for a long time. Herein, we report on the synthesis of 153Sm/166Ho complexes with the novel amino acid-chitosan polymers, N-(γ-propanoylvalin)-chitosan (CHICO-val) and N-(γ-propanoyl-aspartic acid)-chitosan (CHICO-asp). The main goal of this study was to obtain data on the radiochemical and biological behaviour of these complexes and information regarding their therapeutic potential when compared to 153Sm/166Ho-chitosan. Radiolabelling yield of 153Sm/166Ho-amino acid-chitosan complexes was dependent on polymer concentration but less dependent on pH. Radiochemical stability was shown to be higher for amino acid-chitosans than for chitosan, with 153Sm/166Ho-CHICO-val being stable up to 3 h, while 153Sm/166Ho-CHICO-asp is stable up to 24 h. In the presence of ascorbic acid radiochemical stability of 153Sm/ 166Ho-CHICO-val and 153Sm/166Ho-CHICO was improved, decreasing for 153Sm/166Ho-CHICO-asp. In vivo behaviour of 153Sm complexes was studied in mice. The radioactive amino acid-chitosans can be directly injected into blood stream without significant retention on injection site, being trapped by liver. Biodistribution studies suggest that the radioactive amino acid-chitosans, due to its water solubility and stability may be considered potential candidates to be further explored for liver targeted nuclear therapy. Copyright © 2008 John Wiley & Sons, Ltd.