Radiosynthesis and PET Bioimaging of Br-Bedaquiline in a Murine Model of Tuberculosis

Overview

Journal ACS Infect Dis

Specialties Infectious Diseases
Microbiology
Pharmacology

Date 2019 Jul 27

PMID 31345032

Citations 20

Authors

Alvaro A Ordonez

Laurence S Carroll

Sudhanshu Abhishek

Filipa Mota

Camilo A Ruiz-Bedoya

Mariah H Klunk

Alok K Singh

Joel S Freundlich

Ronnie C Mease

Sanjay K Jain

Affiliations

Soon will be listed here.

Abstract

Bedaquiline is a promising drug against tuberculosis (TB), but limited data are available on its intralesional pharmacokinetics. Moreover, current techniques rely on invasive tissue resection, which is difficult in humans and generally limited even in animals. In this study, we developed a novel radiosynthesis for Br-bedaquiline and performed noninvasive, longitudinal whole-body positron emission tomography (PET) in live, -infected mice over 48 h. After the intravenous injection, Br-bedaquiline distributed to all organs and selectively localized to adipose tissue and liver, with excellent penetration into infected lung lesions (86%) and measurable penetration into the brain parenchyma (15%). Ex vivo high resolution, two-dimensional autoradiography, and same section hematoxylin/eosin and immunofluorescence provided detailed intralesional drug biodistribution. PET bioimaging and high-resolution autoradiography are novel techniques that can provide detailed, multicompartment, and intralesional pharmacokinetics of new and existing TB drugs. These technologies can significantly advance efforts to optimize drug dosing.

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