Synthesis,68Ga-Radiolabeling, and PreliminaryIn VivoAssessment of a Depsipeptide-Derived Compound as a Potential PET/CT Infection Imaging Agent

Abstract

Noninvasive imaging is a powerful tool for early diagnosis and monitoring of various disease processes, such as infections. An alarming shortage of infection-selective radiopharmaceuticals exists for overcoming the diagnostic limitations with unspecific tracers such as67/68Ga-citrate or18F-FDG. We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with68Ga for a subsequentin vitroassessment andin vivoinfection imaging usingEscherichia coli-bearing mice by targeting bacterial lipopolysaccharides with PET/CT. Following DOTA-conjugation, the compound was verified for its cytotoxic and bacterial binding behaviour and compound stability, followed by68Gallium-radiolabeling.µPET/CT using68Ga-DOTA-TBIA101 was employed to detect muscularE. coli-infection in BALB/c mice, as warranted by thein vitroresults.68Ga-DOTA-TBIA101-PET detectedE. coli-infected muscle tissue (SUV = 1.3–2.4) > noninfected thighs(P=0.322)> forearm muscles(P=0.092)> background(P=0.021)in the same animal. Normalization of the infected thigh muscle to reference tissue showed a ratio of 3.0 ± 0.8 and a ratio of 2.3 ± 0.6 compared to the identical healthy tissue. The majority of the activity was cleared by renal excretion. The latter findings warrant further preclinical imaging studies of greater depth, as the DOTA-conjugation did not compromise the TBIA101’s capacity as targeting vector.