靶向生长抑素受体各亚型的68Ga/177Lu-PA探针的构建及其在肿瘤个体化诊疗中的研究

不同肿瘤在不同阶段其表达的生长抑素受体(SSTRs)各亚型各有差异. 仅凭核素标记奥曲肽对SSTR2的监测, 已远不能满足肿瘤个体化诊疗的需求. 本项目拟发展出一种具有SSTR1,2,3,5靶向性, 结合诊断/治疗为一体的新型分子探针, 从原理上解决对SSTRs全面显像的问题. 本项目立足于结构修饰, 获得SSTR1,2,3,5高亲和力的新型DOTA-PA肽, 而后分别进行68Ga/177Lu的标记及质量控制, 获得68Ga/177Lu-PA探针. 进一步通过PET/CT实现68Ga-PA活体, 无创, 可视化探测, 获取SSTR高表达肿瘤的功能信息, 分析SSTRs的表达情况与肿瘤进展关系. 通过177Lu-PA探针进行SSTRs高表达肿瘤多肽受体放射性核素治疗的研究工作. 总之, 本项目提出的68Ga/177Lu-PA探针, 有望为临床方面SSTR高表达肿瘤个体化诊疗提供新的依据.

Somatostatin action is mediated by 5 somatostatin receptors (SSTR1-5). Targeted molecular imaging of SSTR2 in neuroendocrine tumors (NET) by nuclide radiolabeling octreotide has been extensively accepted in clinical application and also meets more challenge. One great challenge still remains: comprehensive diagnostic imaging of all SSTR1-5. In this project, we are planning to design novel radio-tracers for noninvasive SSTR receptors imaging. Pasireotide (PA) is a multi ligand somatostatin (SRIF) analog able to bind to SSTR1,2,3,5 subtypes. We firstly synthesized and got a novel DOTA-PA peptide based on the modification of PA. Then, 68Ga/177Lu-PA tracers have been prepared and quality controlled. By means of PET/CT’s high-resolution, tissue localization, 68Ga-PA could provide more functional information about the SSTRs expression in tissues/tumors. 177Lu-PA may used for peptide receptor radionuclide therapy. These results suggest that 68Ga/177Lu-PA might be SSTR-positive tumors imaging agent and further studies are warranted. By the precisely detect the SSTR1,2,3,5 expression, it can prediction efficacy and prognostic evaluation for personalized cancer therapy.