The Development Of Positron Imaging Agents Of Camptothecins-topoisomerase â…  Inhibitor

Camptothecin(CPT)is a natural antitumor alkaloid isolated froom Chinese tree camptotheca acuminate. CPT and many of its derivatives are potent inhibitor of Topoisomerase I(Topo I). Their antitumor mechanism is that CPT and its derivatives could stabilize the Topo I-DNA complex and subsequently influence the republication of DNA and cause the cell death. During the last several decades, thousands of CPT derivatives were synthesized and their antitumor activities were evaluated. Nowadays, several CPT Irinotecan and Belotecan etc have been applied in clinic in and outsid for treating ovarian cancer, small cell lung cancer, colon cancer and gastric cancer owing to their specific action mechanism as inhibitors of Topoisomerase.Based on the preliminary work of Natural Science Foundation of China which CPT derivatives had been organic synthesized,we performed an experiment about the antitumor activity in vitro of the CPT derivatives. Secondly, considering the specific-targeting of Topoisomerase I to the derivatives.three CPT derivatives were selected for the radiochemical synthesis of PET tracers for tumor.It is prerequisite that the structure of the PET tracers should possess some groups which can bear the labeled elements such as18F and nC easily and feasibly.finaly,we innovative synthesized three new PET tracers,[18F]-10-(2-fluoroethoxy)-camptothecin10-[11C]-methoxyl-camptothecin and [18F]-7-P-Fluorobenzoyl-camptothecin.The last section designed a series of biological experiment research for part of the PET tracers,also,we performed Micro-PET imaging with normal ICR mices and tumor bearing mices.