Introduction: The asparagine-glycine-arginine (NGR) peptide sequence which primarily binds to aminopeptidase N (APN/CD13), was found by phage display to exhibit great selectivity for endothelial cells of new vessels (angiogenesis). Objective:The aim of this study was the evaluation of 99mTc-MAG3-cyclic NGRyk peptide as a marker of angiogenesis in different tumor models.

Methods: The conjugated MAG3-NGRyk was radiolabeled with 99mTc, using tartrate buffer. Radiochemical purity was evaluated by HPLC. In vitro studies were conducted using human tumor cells namely prostate (PC3), lung (A549), and ovarian (OVCAR-3). Biodistribution was also evaluated using Nude mice bearing tumors of the same cells, 1h post injection.

Results: Radiochemical purity of the radiotracer was 99.3 ± 0.4%. In vitro studies showed similar uptake in ovarian and lung tumor cells. Biodistribution of 99mTc-MAG3-NGRyK revealed renal excretion, blood uptake in the range of 0.5 ID/ml, and uptake below 1%ID/g in other organs and tissues (Table 1). Tumor uptake ex-vivo was more pronounced in animals bearing ovarian tumor cells, and was 62% blocked, however imaging showed better visualization for lung tumor with ROI value of 2.65%.

Conclusion: The new angiogenesis radiotracer represented by the peptide NGR is a promising candidate for diagnostic applications, particularly in lung cancer. Further studies using this sequence in a homodimer compound and in combination with RGD are envisaged.