Preparation and preclinical evaluation of a (68)Ga-labelled c(RGDfK) conjugate comprising the bifunctional chelator NODIA-Me

BACKGROUND: We recently developed a chelating platform based on the macrocycle 1,4,7-triazacyclononane with up to three, five-membered azaheterocyclic arms for the development of (68)Ga- and (64)Cu-based radiopharmaceuticals. Here, a (68)Ga-labelled conjugate comprising the bifunctional chelator NODIA-Me in combination with the α(v)ß(3)-targeting peptide c(RGDfK) has been synthesized and characterized. The primary aim was to evaluate further the potential of our NODIA-Me chelating system for the development of (68)Ga-labelled radiotracers. RESULTS: The BFC NODIA-Me was conjugated to c(RGDfK) by standard peptide chemistry to obtain the final bioconjugate NODIA-Me-c(RGDfK) 3 in 72% yield. Labelling with [(68)Ga]GaCl(3) was accomplished in a fully automated, cGMP compliant process to give [(68)Ga]3 in high radiochemical yield (98%) and moderate specific activity (~ 8 MBq nmol− (1)). Incorporation of the Ga-NODIA-Me chelate to c(RGDfK) 2 had only minimal influence on the affinity to integrin α(v)ß(3) (IC(50) values [(nat)Ga]3 = 205.1 ± 1.4 nM, c(RGDfK) 2 = 159.5 ± 1.3 nM) as determined in competitive cell binding experiments in U-87 MG cell line. In small-animal PET imaging and ex vivo biodistribution studies, the radiotracer [(68)Ga]3 showed low uptake in non-target organs and specific tumor uptake in U-87 MG tumors. CONCLUSION: The results suggest that the bifunctional chelator NODIA-Me is an interesting alternative to existing ligands for the development of (68)Ga-labelled radiopharmaceuticals.