Test-retest properties of [11C]-PXT012253 as a positron emission tomography (PET) radiotracer in healthy human brain: PET imaging of mGlu4

Background The metabotropic glutamate receptor 4 (mGlu4) has been proposed as a target for Parkinson’s disease to measure levodopa-induced dyskinesia. [ ¹¹ C]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 [ ¹¹ C]PXT012253 in healthy volunteers. Results Six subjects (4 females) completed. [ ¹¹ C]PXT012253 displayed high uptake and rapid wash-out. Unchanged [ ¹¹ C]PXT012253 at 20 min was 10–20%. V _T in subcortical regions was higher than in cortical regions. 2TC provided better fits than 1TC. V _T 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 V _T <7% and ICC > 0.93 using the 2TC, Logan and MA1 graphical analyses. Time stability analysis showed that V _T values estimated using 63 minutes of imaging were within 10% of the values obtained with 93 minutes with all three models. Conclusion [ ¹¹ C]PXT012253 showed a high brain uptake, with rapid washout and metabolism. V _T was reliably estimated using 2TC, Logan GA and MA1. The test-retest metrics showed high replicability, indicating [ ¹¹ C]PXT012253 to be a suitable PET radioligand for mGlu4. EudraCT number: 2018-002333-37 Registered at clinicaltrials.gov NCT03826134 Registered 17 January 2019 https://www.clinicaltrials.gov/study/NCT03826134