64Cu-NODAGA-c(RGDyK) Is a Promising New Angiogenesis PET Tracer: Correlation between Tumor Uptake and Integrin Expression in Human Neuroendocrine Tumor Xenografts

Purpose . The purpose of this paper is to evaluate a new PET tracer 64 Cu-NODAGA-c(RGDyK) for imaging of tumor angiogenesis using gene expression of angiogenesis markers as reference and to estimate radiation dosimetry for humans. Procedures . Nude mice with human neuroendocrine tumor xenografts (H727) were administered 64 Cu-NODAGA-c(RGDyK) i.v. for study of biodistribution as well as for dynamic PET. Gene expression of angiogenesis markers integrin α V , integrin β 3 , and VEGF-A were analyzed using QPCR and correlated to the tracer uptake in the tumors (%ID/g). From biodistribution data human radiation-absorbed doses were estimated using OLINDA/EXM. Results . Tumor uptake was 1.2%ID/g with strong correlations between gene expression and tracer uptake, for integrin α V   R = 0.76, integrin β 3   R = 0.75 and VEGF-A R = 0.81 (all P < 0.05). The whole body effective dose for humans was estimated to be 0.038 and 0.029 mSv/MBq for females and males, respectively, with highest absorbed dose in bladder wall. Conclusion . 64 Cu-NODAGA-c(RGDyK) is a promising new angiogenesis PET tracer with potential for human use.