METHYL (1R,2S,3S,5S)-8-[(E)-4-(18F)FLUORANYLBUT-2-ENYL]-3-(4-METHYLPHENYL)-8-AZABICYCLO[3.2.1]OCTANE-2-CARBOXYLATE

Table of contents

• What is 18F-LBT-999?
• How does 18F-LBT-999 work?
• Which conditions is 18F-LBT-999 being studied for?
• How is 18F-LBT-999 given?
• What do the clinical trials show?

What is 18F-LBT-999?

18F-LBT-999 is an investigational radiotracer, a radioactive substance used in positron emission tomography (PET) imaging to visualise specific proteins in the brain. Its full chemical name is methyl (1R,2S,3S,5S)-8-[(E)-4-(18F)fluoranylbut-2-enyl]-3-(4-methylphenyl)-8-azabicyclo[3.2.1]octane-2-carboxylate. The product record in the EU Clinical Trials Information System lists the product name as 18F-LBT-999 and the authorisation holder as the Institut National de la Santé et de la Recherche Médicale (INSERM).^[1] It has no marketing authorisation in the product records, meaning it is used only in research and not available as a medicine.^[1]

How does 18F-LBT-999 work?

18F-LBT-999 binds to presynaptic dopamine membrane transporters, proteins on the surface of nerve cells that normally reabsorb the chemical messenger dopamine after it has been released. The fluorine-18 atom attached to the molecule emits positrons that a PET scanner detects, allowing researchers to measure how much of the tracer has bound to dopamine transporters in specific brain regions. In the registered trial, the level of binding is expressed as the average binding potential in the striatum, which includes the caudate nuclei and putamen.^[1] This measurement is intended to reveal whether dopaminergic pathways are disrupted after severe traumatic brain injury with coma.

Which conditions is 18F-LBT-999 being studied for?

• Comatose traumatic brain injury — the only registered trial studies people who are in a coma after severe traumatic brain injury, to see whether their dopamine networks show metabolic abnormalities compared with people without brain injury.^[1]

How is 18F-LBT-999 given?

18F-LBT-999 is prepared as a solution for injection and given intravenously. In the registered trial the dose is 3 MBq per kilogram of body weight, administered as a single injection before PET imaging.^[1] The product record notes that in one record the substance is part of a fixed combination, although the trial description does not state what the combination partner is.^[1]

What do the clinical trials show?

One trial is registered for 18F-LBT-999. It is a Phase 4, interventional study authorised to enrol 55 participants with comatose traumatic brain injury, comparing their PET scans with a control group.^[1] The primary outcome is the level of 18F-LBT-999 binding to presynaptic dopamine membrane transporters in the striatum, expressed as the average binding potential, to characterise metabolic abnormalities in the dopaminergic network. The trial is currently authorised but does not report results yet. Because this is a diagnostic imaging study, the measurements concern what the scan shows rather than a clinical benefit from treatment.