Brain imaging to spot active D2 dopamine receptors tied to antipsychotic-related sensitivity in schizophrenia
Official title: Imaging the Functional State of the D2high Receptor in drug induced dopamine supersensitivity in schizophrenia
Funded at Mclean Hospital · NIH-11264828 · Data updated 2026-11-12
This project uses a new PET tracer to detect overactive D2 dopamine receptors that can underlie medication-related sensitivity in people with schizophrenia.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Mclean Hospital NIH-funded |
| Lab location | 1 site (Belmont, United States) |
| Project start | March 1, 2024 |
| Project end | December 31, 2028 |
| Funding year | 2026 |
| Award (this year) | $666,559 |
| NIH project number | 5R01MH134074-03 |
| Project ID | NIH-11264828 on NIH RePORTER |
Who could benefit from this research
✓Could help
Future candidates would be people with schizophrenia who are taking antipsychotics and show signs of increasing medication resistance or suspected dopamine supersensitivity.
✕Less likely to help
People without schizophrenia, those not on antipsychotic medications, or those who cannot undergo PET imaging (for example due to pregnancy or incompatible medical conditions) are unlikely to benefit from this tracer.
What this research studies
Researchers are developing a PET imaging tracer called [18F]MCL-524 that selectively binds the active D2high dopamine receptor implicated in dopamine supersensitivity in schizophrenia. They will perform broad off-target binding screens, ADME studies, and a 14-day toxicology study in rats to confirm safety and specificity. Next, they will measure tracer biodistribution and test-retest reliability with PET scans in rhesus monkeys to confirm brain penetration and reproducibility. This preclinical work aims to complete rigorous characterization before any human imaging is attempted.
Why it matters
Potential benefit: If successful, this could help clinicians detect rising D2high activity early and guide antipsychotic dosing to prevent dopamine supersensitivity and symptom worsening.
How similar studies have gone: Existing PET tracers image D2 receptors broadly, but a highly selective agonist tracer for the active D2high form is novel and has only shown promising preclinical results so far.
Where this research is happening
-
Mclean Hospital
Belmont, United States Active
Researchers
- Principal investigator: Subburaju, Sivan — Mclean Hospital
- Study coordinator: Subburaju, Sivan
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About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page.