Development of survivin imaging agents for the realization of tumor specific nuclear medicine diagnosis

本研究旨在开发survivin靶向放射性药物，实现肿瘤特异性核医学诊断。由于4,6 -二芳基吡啶酮对survivin蛋白二聚体位点具有较高的亲和力，因此合成了几种衍生物并对其进行了评价。在survivin高表达癌细胞的结合实验中，这些4,6 -二芳基吡啶酮衍生物表现出高的膜通透性，并与survivin表达位点具有相似的积累模式。此外，体内生物分布研究表明[^<125> I] 4,6 -二芳基吡啶酮具有中度血潴留和正常组织的快速清除。本研究结果表明，这些4,6 -二芳基吡啶酮可能是有希望的肿瘤显像剂。

In the present study, we aimed to develop survivin targeting radiopharmaceuticals for the realization of tumor specific nuclear medicine diagnosis. Because 4, 6-diaryl pyridinones have been reported to possess high affinity for dimer site of survivin protein, several derivatives were synthesized and evaluated. In the binding assay using the cancer cells with high expression of survivin, these 4, 6-diaryl pyridinone derivatives showed high membrane permeability and similar accumulation pattern with survivin expression site. Furthermore in vivo biodistribution study revealed that[^<125> I] 4, 6-diaryl pyridinones showed moderate blood retention and rapid clearance by normal tissues. The results of this study illustrate that these 4, 6-diaryl pyridinones might be promising tumor imaging agents for survivin.