68Ga-NODAGA-RGD is a suitable substitute for 18F-Galacto-RGD and can be produced with high specific activity in a cGMP/GRP compliant automated process

Introduction: F-18-Galacto-cyclo(RGDN) is a well investigated tracer for imaging of alpha nu beta 3 expression in vivo, but suffers from the drawback of a time consuming multistep synthesis that can hardly be established under GMP conditions. In this study, we present a direct comparison of the pharmacokinetic properties of this tracer with Ga-68-NODAGA-cyclo(RGDyK), in order to assess its potential as an alternative for F-18-Galacto-cyclo(RGDfK). Methods: Ga-68 labeling of NODAGA-cyclo(RGDyK) was done in full automation using HEPES-buffered eluate of an SnO2 based Ga-68-generator. Using M21 (human melanoma) xenografted BALB/c nude mice, biodistribution studies and micro-PET scans were performed for both F-18-Galacto-cyclo(RGM) and Ga-68-NODAGA-cyclo(RGDyK), and for the latter, in vivo stability was assessed. IC50 was determined in a displacement assay on M21 cells against I-125-echistatin. Results: Ga-68-NODAGA-cyclo(RGDyK) was produced with high specific activity (routinely ca. 500 GBq/mu mol) within 15 min. IC50 values are similar for both substances. Tracer uptake was similar in alpha nu beta 3 positive tumors (1.45% +/- 0.11% ID/g and 1.35% +/- 0.53% ID/g for Ga-68-NODAGA-RGD and F-18-Galacto-RGD, respectively) as well as for all other organs and tissues, with the exception of gall bladder and intestines, where F-18-Galacto-cyclo(RGDfK) uptake was significantly higher, which can be explained by the higher hydrophilicity of Ga-68-NODAGA-cyclo(RGDyK) (logP= -4.0 vs. -3.2 for F-18-Galacto-RGD). Only intact tracer was detected 30 min p.i. in organs and tumor; however, minor amounts of metabolites were found in the urine (6% of total urine activity). Conclusion: Ga-68-labeling of NODAGA-RGD can be performed rapidly and efficiently within 15 min in a GMP compliant process. Similar preclinical results were obtained in comparison with F-18-Galacto-RGD. Therefore, Ga-68-NODAGA-cyclo(RGDyK) is a suitable replacement for F-18-Galacto-cyclo(RGDfX). (C) 2012 Elsevier Inc. All rights reserved.