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Development of an MgluR4 PET Radioligand

Study Rationale:                   
mGluR4 is a glutamate receptor that is believed to be a potential therapeutic target for Parkinson’s disease (PD). Developing an imaging tracer may allow researchers to quantify this receptor in subjects with the disease. In addition a tracer will be critical in determining dosing of drugs that are developed toward this target.

We hypothesize that a radiolabeled compound will allow researchers to measure the quantity of the mglur4 receptor in pre-clinical models.

Study Design:
From research performed by Prexton Therapeutics, a large number of compounds with high affinity have been discovered. We will label with Fluorine-18 the compounds with the best affinity and using a PET scanner to evaluate their distribution pre-clinically.

Impact on Diagnosis/Treatment of Parkinson’s Disease:             
While a decrease in dopamine is the most recognized neurochemical change in the brain in PD, studies have recently shown that other non-dopamine neurochemicals also play an important role. The development of an imaging tracer for mGlur4 will provide an extremely useful tool to improve our understanding of the role of the glutaminergic pathway in individuals with PD and will be a critical component of drug development.  

Next Steps for Development:
After screening and identifying the best compound in pre-clinical models, we will perform test/retest and dose occupancy studies.

Final Outcome

The primary objective of this study was to characterize brain penetration and uptake of two radiotracers in pre-clinical Parkinson's models. Both tracers showed very low brain uptake with no visible regional specificity. Intravenous administration did not produce any clear evidence of any effect on vital sign.

October 2015


  • Francois Conquet, PhD

    Geneva Switzerland

  • Gilles Tamagnan, PhD

    New Haven, CT United States

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