Preclinical Assessment of a 68Ga-DOTA-Functionalized Depsipeptide as a Radiodiagnostic Infection Imaging Agent

Abstract

The study assessed a radiolabeled depsipeptide conjugate (68Ga-DOTA-TBIA101) for its potential as an imaging agent targeting infection or infection-associated inflammation. 68Ga-labeled DOTA-TBIA101 imaging was performed in (NZR1) healthy rabbits; (NZR2) rabbits bearing muscular sterile inflammation and Staphylococcus aureus (SA) infection; and (NZR3) rabbits infected with Mycobacterium tuberculosis (MTB) combined with a subcutaneous scruff infection of SA in the same animal. All animals were imaged using a PET/CT scanner at 5 and 60 min post injection. Images showed elevated accumulation of 68Ga-DOTA-TBIA101 in the sterile muscular inflammation site (T/NT ratio = 2.6 ± 0.37 (5 min) and 2.8 ± 2.3 (60 min)) and muscles infected with MTB (T/NT ratio = 2.6 ± 0.35 (5 min) and 2.8 ± 0.16 (60 min)). The findings suggest that 68Ga-DOTA-TBIA101-PET/CT may detect MTB-associated inflammation, although more foundational studies need to be performed to rationalize the diagnostic value of this technique.

An update on radiotracer development for molecular imaging of bacterial infections

“…Depsidomycin itself is a natural AMP isolated from S. lavendofolae and exhibits antimicrobial activities against i.e., drug-resistant M. tuberculosis [80]. As a tracer, 68 Ga-DOTA-TBIA101 detected muscular E. coli infections in mice with abscessto-muscle ratios between 1.2 and 1.6 [81], S. aureus (with a target-to-nontarget ratio between 1.2 and 1.3), and M. tuberculosis (abscess-to-muscle ratios between 2.0 and 2.8) infections in rabbits [82]. These results indicate a preference for infections with M. tuberculosis, but unfortunately the tracer also accumulated at sites of sterile inflammation which limits its translational potential.…”

Peptide-Based Drugs and Drug Delivery Systems

“…In particular, the interaction of AMPs with bacterial membranes may be exploited to design imaging agents for targeting bacterial infection. Ebenhan et al [ 14 ] report their pioneering study in this particular topic, by using a radiolabeled depsipeptide conjugate to explore its potential as a radiodiagnostic agent for the imaging of infection.…”

PET Radiopharmaceuticals for Specific Bacteria Imaging: A Systematic Review

“…Furthermore, a similarly increased uptake with T/NT ratio of 2.6 was also found in sterile inflammation. Thus, these results suggest a lack of bacterial selectivity for TBIA101 and therefore a limited usefulness in specific bacterial imaging [38].…”