Radiolabeling and Preliminary Evaluation of Ga-68 Labeled NODAGA-Ubiquicidin Fragments for Prospective Infection Imaging

Abstract

The present work was aimed at the development of prospective positron emission tomography (PET)agents for infection imaging. Towards this aim, ubiquicidin (UBI) fragments conjugated with the macrocyclic NODAGA chelator were radiolabeled with Ga-68 and evaluated. Conformations of custom synthesized NODAGA-UBI (29-41) and NODAGA-UBI (31-38) conjugates were compared with UBI (29-41) by circular dichroism (CD) spectroscopy. Optimization of labeling of NODAGA conjugates of UBI peptides with Ga-68 was performed and quality control analysis was carried out by chromatography techniques. In vitro uptake of [68Ga] NODAGA-UBI (29-41) and [68Ga]NODAGA-UBI (31-38) was studied in Staphylococcus aureus cells. In vivo distribution of [68Ga]GaCl3 and [68Ga]NODAGA-UBI complexes was performed in normal Swiss mice. Conformations of NODAGA-UBI (29-41) and NODAGA-UBI (31-38) conjugates were found to be similar to UBI (29-41). NODAGA-UBI conjugates could be consistently labeled with Ga-68 in high radiochemical yields (>95%) with high radiochemical purity (>95%). [68Ga]NODAGA-UBI (29-41) and [68Ga]NODAGA-UBI (31-38) complexes showed retention time of 14 and 14.5min, respectively, by HPLC radiochromatogram. Specific uptake of [68Ga]NODAGA-UBI fragments was observed in S.aureus cells. Greater than 64% of the injected dose was cleared via the renal route at 1h post injection, and no significant uptake in vital organs of mice was observed with both the agents. This is the first report on Ga-68 labeled NODAGA-UBI fragments for infection imaging and the agents hold tremendous prospect in PET imaging.