【摘 要】
：
Objectives:Anticancer therapies with vascular disrupting agents (VDAs) or radiofrequency ablation (RFA) can noninvasively or minimum-invasively induce tumor necrosis but often leave viable residues le
【机 构】
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Catholic University Leuven Belgium
【出 处】
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中国上海第七届国际新药发明科技年会
论文部分内容阅读
Objectives:Anticancer therapies with vascular disrupting agents (VDAs) or radiofrequency ablation (RFA) can noninvasively or minimum-invasively induce tumor necrosis but often leave viable residues leading to failure in cancer cure.Exploiting the extraordinary targetability of our newly discovered necrosis-avid compounds with an in vivo target-to-nontarget ratio over 30 superior to monoclonal antibody approaches,we sought to develop a strategy of dual targeting cancer theragnostics for improved treatability or curability of malignant tumors.Methods:Two lead compounds in this experiment are naturally extractable and synthetically derivable,about 100 times smaller in MW than monoclonal antibodies,and already in use as medicines.The first compound Combretastatin A4 phosphate (CA4P) was intravenously injected at 10 mg/kg for causing selective tumor vascular shutdown and ischemic necrosis.The second necrosis avid compound hypericin was labeled with iodine-131 to form monoiodohypericin (13 1I-MIH) and intravenously injected at 10 mCi/kg to kill residual tumor cells by crossfire irradiation.Rats with liver tumors were divided into 4 groups:group A with 2 vehicles,B and C with CA4P and 13 II-MIH respectively,and D with CA4P plus 131I-MIH.Therapeutic efficacy was monitored by in vivo imaging and ex vivo autoradiography and histology.Biodistribution of 131I-MIH was radioactively quantified.
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