Studies on the Biological Behaviors of Taxol Derivatives

Awh, Ok Doo; Yoo, Dae Wung; Im, Sang Moo

Abstract

This study was designed to prospect the 'In-labelled paclitaxel as tumor imaging agent. In order to provide a taxol molecule with a functional group which is able to chelate In-lll, taxol-DTPA conjugate and 2-hemisuccinyltaxol were synthesized by esterification of taxol at C-2 on C-13 carbon with DTPA anhydride and succinic anhydride, respectively. Synthesis yield of the taxol derivatives was 34% for taxol- DTPA and 80% for 2'-hemisuccinyltaxol. Cytotoxicity of the taxol derivatives were measured by MTT method toward cell lines HT29, B16, P388, and CT26. The cytotoxic activities of the taxol derivatives were maintained, although less active than taxol. Radiolabelling of the taxol derivatives were proceeded directly with 111InCh or indirectly with 111In-citrate(ligand-exchange method). The ligand-exchane methocl was not suitable because some precipitat:es appeared during the reaction. On the contrary, by direct radiolabelling methnd, we were able to obtain taxol DTPA-111In in 100% radiochemical yield. However, 2'-hemisuccinyltaxol was not labellecl by both methods. Yield and radiochemiral purity of the radiolabelled com- pound were determined by HPI.C, paper chromatography and instant thin layer chromatography. Taxol-DTPA-111In was characterized to be hydrophilic by lipophi- licity test, and nearly non-adhesive to HT29, E316, P388, and CT26 by cell hinding affinity test. Binding affinity of the taxol-DTPA-111In complex to serum proteins was also examined by protein precipitation with 30% trichloroacetic acid. The results showed that 309o of the taxol-DTPA-111In complex binds with serum proteins.