Evaluation of ¹⁸⁸Re-labeled NGR–VEGI protein for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts

Vascular endothelial growth inhibitor (VEGI) is an anti-angiogenic protein, which includes three isoforms: VEGI-174, VEGI-192, and VEGI-251. The NGR (asparagine–glycine–arginine)-containing peptides can specifically bind to CD13 (Aminopeptidase N) receptor which is overexpressed in angiogenic blood vessels and tumor cells. In this study, a novel NGR–VEGI fusion protein was prepared and labeled with ¹⁸⁸Re for radioimaging and radiotherapy in mice bearing human fibrosarcoma HT-1080 xenografts. Single photon emission computerized tomography (SPECT) imaging results revealed that ¹⁸⁸Re-NGR–VEGI exhibits good tumor-to-background contrast in CD13-positive HT-1080 tumor xenografts. The CD13 specificity of ¹⁸⁸Re-NGR–VEGI was further verified by significant reduction of tumor uptake in HT-1080 tumor xenografts with co-injection of the non-radiolabeled NGR–VEGI protein. The biodistribution results demonstrated good tumor-to-muscle ratio (4.98 ± 0.25) of ¹⁸⁸Re-NGR–VEGI at 24 h, which is consistent with the results from SPECT imaging. For radiotherapy, 18.5 MBq of ¹⁸⁸Re-NGR–VEGI showed excellent tumor inhibition effect in HT-1080 tumor xenografts with no observable toxicity, which was confirmed by the tumor size change and hematoxylin and eosin (H&E) staining of major mouse organs. In conclusion, these data demonstrated that ¹⁸⁸Re-NGR–VEGI has the potential as a theranostic agent for CD13-targeted tumor imaging and therapy.