N,N-DIETHYL-(2-(4-(2-(18F)FLUOROETHOXY)PHENYL)-5,7-DIMETHYLPYRAZOLO(1,5-A)PYRIMIDINE-3-YL)ACETAMIDE

Table of contents

• What is 18F-DPA-714?
• How does 18F-DPA-714 work?
• Which conditions is 18F-DPA-714 studied for?
• How is 18F-DPA-714 given?
• What do the clinical trials show?
• What side effects are known?

What is 18F-DPA-714?

18F-DPA-714 is an investigational radioactive tracer, also known by its full chemical name N,N-DIETHYL-(2-(4-(2-(18F)FLUOROETHOXY)PHENYL)-5,7-DIMETHYLPYRAZOLO(1,5-A)PYRIMIDINE-3-YL)ACETAMIDE. It is a solution for injection given intravenously and is used in positron emission tomography (PET) imaging to visualise inflammation in the brain.^[3] The substance has no marketing authorisation in the product records, meaning it remains an investigational agent supplied by the Centre Hospitalier Universitaire de Toulouse.^[3] In the registry data, 18F-DPA-714 appears as the test substance in two trials, and in two product records it is part of a fixed combination.^[3]

How does 18F-DPA-714 work?

18F-DPA-714 binds to the translocator protein (TSPO), which is present at higher levels when brain immune cells are activated. By attaching a radioactive fluorine-18 atom to the molecule, the tracer can be detected by a PET scanner. This allows researchers to map areas of neuroinflammation in the brain without taking a tissue sample. The primary outcome of the Phase 3 trial in depression measures TSPO density as the cerebral distribution volume of the tracer.^[3] In the intracerebral hemorrhage trial, binding is measured as the mean standard uptake value ratio (SUVR) within the perihematomal edema.^[1] In autoimmune encephalitis, the whole-brain binding potential is calculated using an automated clustering method.^[2]

Which conditions is 18F-DPA-714 studied for?

• Depressive disorder — a Phase 3 trial is comparing neuroinflammation patterns between patients with a current major depressive episode, patients in remission, and healthy controls.^[3]
• Intracerebral hemorrhage — a Phase 2 trial is evaluating whether neuroinflammation around the bleeding site predicts functional outcome at six months.^[1]
• Autoimmune encephalitis — a Phase 2 trial is testing whether the tracer can detect brain inflammation in this immune-mediated condition compared with healthy controls.^[2]

How is 18F-DPA-714 given?

18F-DPA-714 is given as an intravenous injection. The pharmaceutical form is a solution for injection.^[3] In the Phase 3 depression trial, the administered activity is 370 megabecquerels (MBq).^[3] In the two Phase 2 trials, the dose is 3.5 MBq per kilogram of body weight.^[1][2] After injection, participants undergo a PET scan to measure tracer uptake in the brain.

What do the clinical trials show?

Three interventional trials are registered for 18F-DPA-714. The largest is a Phase 2 trial in intracerebral hemorrhage with 117 participants, authorised but not yet reporting results.^[1] The smallest is a Phase 2 trial in autoimmune encephalitis with 20 participants, also authorised.^[2] The only completed trial is a Phase 3 study in depressive disorder with 60 participants.^[3] None of the registry records include published efficacy results; the trials primarily measure tracer binding as a marker of neuroinflammation.

The Phase 3 depression trial compares three groups: patients with a current major depressive episode, patients in remission for at least eight weeks on antidepressants, and healthy controls matched by age and gender.^[3] The primary endpoint is the cerebral distribution volume of [18F]DPA-714 as a measure of TSPO density.^[3] The intracerebral hemorrhage trial measures tracer binding within the perihematomal edema at day 10 and correlates it with functional outcome on the modified Rankin scale at six months.^[1] The autoimmune encephalitis trial measures whole-brain binding potential compared with healthy controls.^[2]

What side effects are known?

No side effect data are reported in the registry records for these trials. As an investigational radioactive tracer, the safety profile is still being evaluated in the ongoing and completed studies.