Synthesis and Biological Evaluation of a Novel ⁶⁸ Ga-Labeled Ubiquicidin 29–41 Complex for PET Imaging of Bacterial Infections

The persistent challenge of bacterial infections in clinical practice necessitates the development of precise diagnostic tools capable of differentiating infectious and inflammatory processes. This study presents the development and evaluation of [⁶⁸Ga]Ga-NOTA-UBI 29-41, a novel PET radiotracer designed for specific bacterial infection imaging. The tracer was synthesized through ⁶⁸Ga-labeling of a NOTA-conjugated ubiquicidin 29-41 derivative, demonstrating excellent radiochemical properties and good <i>in vitro</i> stability in both saline and mouse serum. <i>In vitro</i> binding assays confirmed specific targeting of <i>Staphylococcus aureus</i>, while <i>in vivo</i> studies in mice models revealed significantly higher uptake in infected versus inflamed muscle tissue (<i>p</i> < 0.01). MicroPET imaging further validated the tracer's ability to selectively accumulate at infection sites, with pharmacokinetic analysis showing predominant renal clearance and rapid blood clearance kinetics. These findings collectively demonstrate the potential of [⁶⁸Ga]Ga-NOTA-UBI 29-41 as a clinically translatable agent for accurate discrimination between bacterial infections and sterile inflammation.