18F-Galacto-cyclo(RGDfK) is a well investigated tracer for imaging of ανβ3 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 68Ga-NODAGA-cyclo(RGDyK), in order to assess its potential as an alternative for 18F-Galacto-cyclo(RGDfK).
Methods
68Ga labeling of NODAGA-cyclo(RGDyK) was done in full automation using HEPES-buffered eluate of an SnO2 based 68Ga-generator. Using M21 (human melanoma) xenografted BALB/c nude mice, biodistribution studies and micro-PET scans were performed for both 18F-Galacto-cyclo(RGDfK) and 68Ga-NODAGA-cyclo(RGDyK), and for the latter, in vivo stability was assessed. IC50 was determined in a displacement assay on M21 cells against 125I-echistatin.
Results
68Ga-NODAGA-cyclo(RGDyK) was produced with high specific activity (routinely ca. 500 GBq/μmol) within 15 min. IC50 values are similar for both substances. Tracer uptake was similar in ανβ3 positive tumors (1.45% ± 0.11% ID/g and 1.35% ± 0.53% ID/g for 68Ga-NODAGA-RGD and 18F-Galacto-RGD, respectively) as well as for all other organs and tissues, with the exception of gall bladder and intestines, where 18F-Galacto-cyclo(RGDfK) uptake was significantly higher, which can be explained by the higher hydrophilicity of 68Ga-NODAGA-cyclo(RGDyK) (logP = −4.0 vs. − 3.2 for 18F-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
68Ga-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 18F-Galacto-RGD. Therefore, 68Ga-NODAGA-cyclo(RGDyK) is a suitable replacement for 18F-Galacto-cyclo(RGDfK).