PET imaging of VEGFR and integrins in glioma tumor xenografts using 89Zr labelled heterodimeric peptide

Vascular endothelial growth factor receptor (VEGFR) and integrin av 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-89) for PET imaging of glioma. Zr-89-DFO-heterodimeric peptide, a the newly developed probe, was prepared with radiochemical yield of 88.7 +/- 2.4%. Targeted binding capability of (ZrDFO)-Zr-89-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-89-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-89-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-89-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.

Automated summary

This study developed a novel heterodimeric peptide probe for glioma targeting and PET imaging. The designed probe showed good targeting ability and imaging effect, making it a potential radiopharmaceutical probe for glioma.