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

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.

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.

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。本课题通过对帕瑞泰（pasireotide）进行结构修饰，连接上可进行放射性核素标记的双功能连接剂后采用68Ga、64Cu、177Lu的核素进行了放射性标记，通过体内外实验验证了其靶向性和特异性。由于一种化合物可同时进行多种核素的标记，从而可以实现特异性靶向SSTR1,2,3,5的放射性诊疗一体化。与DOTATATE一起，实现肿瘤生长抑素受体的全覆盖。