Positron Emission Tomography Imaging of Vascular Endothelial Growth Factor Receptor Expression with a new 64Cu labeled peptide

Objectives: Noninvasive positron emission tomography (PET) imaging of vascular endothelial growth factor receptor 2 (VEGFR-2) expression could be a valuable tool for evaluation of patients with a variety of malignancies, and particularly for monitoring those undergoing antiangiogenic therapies that block VEGF/VEGFR-2 function. VEGF125-136 (QKRKRKKSRYKS) is a 12 amino acid peptide encoded by exon 6 of VEGF-A which was first identified as an effective inhibitor to VEGFR-2. The aim of this work was to develop and evaluate in mice the 64Cu labelled analogue as an in vivo tracer for VEGFR-2 expression in solid tumours.Methods: VEGF125-136 was conjugated with PEG3 and DOTA and then labeled with 64Cu (denoted as [64Cu]VEGF125-136) for small-animal PET of mice bearing B16F10 human melanoma cells, U87MG human glioblastoma cells, and MDA-231 human breast cancer xenografts. Biodistribution studies, autoradiography and immunofluorescence staining were carried out to confirm the noninvasive imaging results.Results: The radiolabeling yield and specific activity of [64Cu]VEGF125-136 were more than 95% and 74.3 ± 3.8 GBq/µmol, respectively. Noninvasive microPET showed that [64Cu]VEGF125-136 had variable uptake in different tumors, with the order: B16F10 > U87MG > MDA-231. The pattern of radiotracer uptake was correlated well with variations in VEGFR-2 expression determined ex vivo by immunohistochemical analysis. Moreover, the tracer showed high tumor uptake (5.89 ± 2.58 %ID/g at 20 min postinjection in B16F10 mice) and excellent pharmacokinetics, achieving the maximum imaging quality within 1 h after injection. Biodistribution studies and autoradiography confirmed the VEGFR-2 specificity of [64Cu]VEGF125-136.Conclusions: We have developed a VEGFR-2-specific PET tracer, [64Cu]VEGF125-136. This tracer may be translated into the clinic for imaging tumor angiogenesis and monitoring antiangiogenic treatment efficacy.SNMMI 2020 Annual Meetin