Liu Weihao, Ma Huan, Li Feize, Cai Huawei, Liang Ranxi, Chen Xijian, Lan Tu, Yang Jijun, Liao Jiali, Yang Yuanyou, Liu Ning
Key Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, PR China.
Key Laboratory of Radiation Physics and Technology of the Ministry of Education, Institute of Nuclear Science and Technology, Sichuan University, Chengdu 610064, PR China.
Bioorg Med Chem. 2022 Apr 1;59:116677. doi: 10.1016/j.bmc.2022.116677. Epub 2022 Feb 22.
Vascular endothelial growth factor receptor (VEGFR) and integrin αv are over-expressed in angiogenesis of variety malignant tumors with key roles in angiogenesis, and have been proven as valuable targets for cancer imaging and treatment. In this study, a heterodimeric peptide targeting VEGFR and integrin was designed, and radiolabeled with zirconium-89 (Zr) for PET imaging of glioma. Zr-DFO-heterodimeric peptide, a the newly developed probe, was prepared with radiochemical yield of 88.7 ± 2.4%. Targeted binding capability of Zr-DFO-heterodimeric peptide towards U87MG cells was investigated in murine glioma xenograft models, which shows that the designed probe has good binding ability to both targeting sites. Biodistribution indicated that kidney metabolism is the main pathway and tumor uptake of Zr-DFO-heterodimeric peptide reached the peak of 0.62 ± 0.10% ID/g . U87MG xenograft could be clearly visualized by microPET/CT imaging through 1 to 3 h post-injection of Zr-DFO-heterodimeric peptide. Importantly, the tumor radiouptake was significantly reduced after blocking, and the imaging effect of this radioactive compound was more obvious than that of monomeric peptide probes. Zr-DFO-heterodimeric peptide has been demonstrated to show potential as a new radiopharmaceutical probe towards glioma, and multi-target probes do have advantages in tumor imaging.
血管内皮生长因子受体（VEGFR）和整合素αv在多种恶性肿瘤的血管生成中过度表达，在血管生成中起关键作用，并且已被证明是癌症成像和治疗的有价值靶点。在本研究中，设计了一种靶向VEGFR和整合素的异二聚体肽，并用锆-89（Zr）进行放射性标记用于胶质瘤的PET成像。新开发的探针Zr-DFO-异二聚体肽的制备放射化学产率为88.7±2.4%。在小鼠胶质瘤异种移植模型中研究了Zr-DFO-异二聚体肽对U87MG细胞的靶向结合能力，结果表明所设计的探针对两个靶向位点均具有良好的结合能力。生物分布表明肾脏代谢是主要途径，Zr-DFO-异二聚体肽的肿瘤摄取在注射后1至3小时达到峰值，为0.62±0.10% ID/g。注射Zr-DFO-异二聚体肽后1至3小时，通过microPET/CT成像可以清晰地观察到U87MG异种移植瘤。重要的是，阻断后肿瘤放射性摄取显著降低，且该放射性化合物的成像效果比单体肽探针更明显。Zr-DFO-异二聚体肽已被证明具有作为一种针对胶质瘤的新型放射性药物探针的潜力，并且多靶点探针在肿瘤成像中确实具有优势。
