Delving into the Latest Updates on F-18 quinoline with Synapse

Overview

Basic Info

Drug Type

Small molecule drug, Radiopharmaceuticals and diagnostic agent

Synonyms

F-18 HOQ

Target

APP

Mechanism

APP modulators(Beta amyloid A4 protein modulators), PET imaging(Positron-emission tomography enhancers)

Therapeutic Areas

Nervous System Diseases

Active Indication

Alzheimer Disease

Inactive Indication-

Originator Organization

The University of Texas at Dallas

Active Organization

The University of Texas at Dallas

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Tuberculosis (TB) remains a leading cause of death, but antibiotic treatments for tuberculous meningitis, the deadliest form of TB, are based on those developed for pulmonary TB and not optimized for brain penetration. Here, we perform first-in-human dynamic ¹⁸F-pretomanid positron emission tomography (PET) in eight human subjects to visualize ¹⁸F-pretomanid biodistribution as concentration-time exposures in multiple compartments (NCT05609552), demonstrating preferential brain versus lung tissue partitioning. Preferential, antibiotic-specific partitioning into brain or lung tissues of several antibiotics, active against multidrug resistant (MDR) Mycobacterium tuberculosis strains, are confirmed in experimentally-infected mice and rabbits, using dynamic PET with chemically identical antibiotic radioanalogs, and postmortem mass spectrometry measurements. PET-facilitated pharmacokinetic modeling predicts human dosing necessary to attain therapeutic brain exposures. These data are used to design optimized, pretomanid-based regimens which are evaluated at human equipotent dosing in a mouse model of TB meningitis, demonstrating excellent bactericidal activity without an increase in intracerebral inflammation or brain injury. Importantly, several antibiotic regimens demonstrate discordant activities in brain and lung tissues in the same animal, correlating with tissue antibiotic exposures. These data provide a mechanistic basis for the compartmentalized activities of antibiotic regimens, with important implications for developing treatments for meningitis and other infections in compartments with unique antibiotic penetration.

100 Deals associated with F-18 quinoline

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