NeuralCipher Research overview
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BACKGROUND: The metabotropic glutamate receptor 4 (mGlu4) has been proposed as a target for Parkinson’s disease to measure levodopa-induced dyskinesia. [11C]PXT012253 is a PET radioligand for mGlu4 (3.4 nM), previously characterized in non-human primates. We aimed to determine the optimal method for quantification, duration for acquisition, and test-retest reliability of the binding parameters for [11C]PXT012253 in healthy volunteers. RESULTS: Six subjects (4 females) completed. [11C]PXT012253 displayed high uptake and rapid wash-out. Unchanged [11C]PXT012253 at 20 min was 10–20%. VT in subcortical regions was higher than in cortical regions. 2TC provided better fits than 1TC. VT by Logan GA and MA1 analysis correlated with that of 2TC-CM. MA1 showed better identifiability and standard error than Logan. The test-retest metrics in pons, putamen and thalamus showed absolute variability of VT 0.93 using the 2TC, Logan and MA1 graphical analyses. Time stability analysis showed that VT values estimated using 63 min of imaging were within 10% of the values obtained with 93 min with all three models. CONCLUSION: [11C]PXT012253 showed a high brain uptake, with rapid washout and metabolism. VT was reliably estimated using 2TC, Logan GA and MA1. The test-retest metrics showed high repeatability, indicating [11C]PXT012253 to be a suitable PET radioligand for mGlu4.
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