Positron Emission Tomography Imaging of Infection Using a Nitro-Prodrug Analogue of 2-[F]F--Aminobenzoic Acid

Overview

Journal ACS Infect Dis

Specialties Infectious Diseases
Microbiology
Pharmacology

Date 2020 Jul 17

PMID 32672928

Citations 11

Authors

Yong Li

Fereidoon Daryaee

Grace E Yoon

Doyoung Noh

Peter M Smith-Jones

Yuanyuan Si

Stephen G Walker

Nashaat Turkman

Labros Meimetis

Peter J Tonge

Affiliations

Soon will be listed here.

Abstract

Deep-seated bacterial infections caused by pathogens such as are difficult to diagnose and treat and are thus a major threat to human health. In previous work we demonstrated that positron emission tomography (PET) imaging with 2-[F]F--aminobenzoic acid (2-[F]F-PABA) could noninvasively identify, localize, and monitor infection with excellent sensitivity and specificity in a rodent soft tissue infection model. However, 2-[F]F-PABA is rapidly N-acetylated and eliminated, and in an attempt to improve radiotracer accumulation in bacteria we adopted a prodrug strategy in which the acid was protected by an ester and the amine was replaced with a nitro group. Metabolite analysis indicated that the nitro group of ethyl 2-[F]fluoro-4-nitrobenzoate (2-[F]F-ENB) is converted to the corresponding amine by bacteria-specific nitroreductases while the ester is hydrolyzed into the acid. PET/CT imaging of 2-[F]F-ENB and the corresponding acid 2-[F]F-NB in a rat soft tissue infection model demonstrated colocalization of the radiotracer with the bioluminescent signal arising from Xen29, and demonstrated that the tracer could differentiate infection from sterile inflammation. Significantly, the accumulation of both 2-[F]F-ENB and 2-[F]F-NB at the site of infection was 17-fold higher than at the site of sterile inflammation compared to 8-fold difference observed for 2-[F]F-PABA, supporting the proposal that the active radiotracer is 2-[F]F-NB. Collectively, these data suggest that 2-[F]F-ENB and 2-[F]F-NB have the potential for translation to humans as a rapid, noninvasive diagnostic tool to identify and localize infections.

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