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

• Published in: EJNMMI radiopharmacy and chemistry 2018-05, Vol.3 (1), p.6-6, Article 6
• Main Authors: Läppchen, Tilman, Holland, Jason P., Kiefer, Yvonne, Bartholomä, Mark D.
• Format: Article
• Language: English
• Subjects: Bifunctional chelator; Gallium-68; Imaging; Integrins; Medicine; Medicine & Public Health; Molecular Medicine; NODIA-Me; Nuclear Chemistry; Nuclear Medicine; Peptides; PET imaging; Pharmaceuticals; Pharmacotherapy; Radioactive tracers; Radioisotopes; Radiology; Research Article; αvß3
• ISSN: 2365-421X; 2365-421X
• DOI: 10.1186/s41181-018-0043-2

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.