Gallium-68 labeled Ubiquicidin derived octapeptide as a potential infection imaging agent

Gallium-68 based infection imaging agents are in demand to detect infection foci with high spatial resolution and sensitivity. In this study, Ubiquicidin derived octapeptide, UBI (31-38) conjugated with macrocyclic chelator NOTA was radiolabeled with ⁶⁸Ga to develop infection imaging agent.

Circular dichroism (CD) spectroscopy was performed to study conformational changes in UBI (31-38) and its NOTA conjugate in a "membrane like environment". Radiolabeling of NOTA-UBI (31-38) with ⁶⁸Ga was optimized and quality control analysis was done by chromatography techniques. In vitro evaluation of ⁶⁸Ga-NOTA-UBI (31-38) in S. aureus and preliminary biological evaluation in animal model of infection was studied. Initial clinical evaluation in three patients with suspected infection was carried out.

⁶⁸Ga-NOTA-UBI (31-38) was prepared in high radiochemical yields and high radiochemical purity. In vitro evaluation of ⁶⁸Ga-NOTA-UBI (31-38) complex in S. aureus confirmed specificity of the agent for bacteria. Biodistribution studies with ⁶⁸Ga-NOTA-UBI (31-38) revealed specific uptake of the complex in infected muscle compared to inflamed muscle with T/NT ratio of 3.24 ± 0.7 at 1 h post-injection. Initial clinical evaluation in two patients with histopathologically confirmed infective foci conducted after intravenous injection of 130-185 MBq of ⁶⁸Ga-NOTA-UBI (31-38) and imaging at 45-60 min post-injection revealed specific uptake at the sites of infection and clearance from vital organs. No uptake of tracer was observed in suspected infection foci in one patient, which was proven to be aseptic and served as negative control.

This is the first report on ⁶⁸Ga labeled NOTA-UBI (31-38) fragment for prospective infection imaging.