Synthesis, 68Ga-Radiolabeling, and Preliminary In Vivo Assessment of a Depsipeptide-Derived Compound as a Potential PETCT Infection Imaging Agent

Abstract EN

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 as 67/68Ga-citrate or 18F-FDG.

We report here TBIA101, an antimicrobial peptide derivative that was conjugated to DOTA and radiolabeled with 68Ga for a subsequent in vitro assessment and in vivo infection imaging using Escherichia 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 by 68Gallium-radiolabeling.

µPET/CT using 68Ga-DOTA-TBIA101 was employed to detect muscular E.

coli-infection in BALB/c mice, as warranted by the in vitro results.

68Ga-DOTA-TBIA101-PET detected E.

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.