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

• Published in: EJNMMI research Vol. 15; no. 1; pp. 71 - 10
• Main Authors: Stenkrona, Per, Arakawa, Ryosuke, Guo, Jiamei, Bang-Andersen, Benny, Nag, Sangram, Moein, Mohammad Mahdi, Jia, Zhisheng, Cselenyi, Zsolt, Halldin, Christer, Varrone, Andrea
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 14.06.2025; Springer Nature B.V; SpringerOpen
• Subjects: [11C]PXT012253; Brain; Brain research; Cardiac Imaging; Catheters; Dyskinesia; Ethics; Human brain; Imaging; Ligands; Medical imaging; Medicine; Medicine & Public Health; mGlu4; Nuclear Medicine; Oncology; Original Research; Orthopedics; Parkinson's disease; Positron emission; Positron emission tomography (PET); Radioactive tracers; Radiology; Schizophrenia; Stability analysis; Standard error; Test-retest; Thalamus; Tomography; Test-retest; C]PXT012253; mGlu4; Human brain; Positron emission tomography (PET); [; [11C]PXT012253
• ISSN: 2191-219X; 2191-219X
• DOI: 10.1186/s13550-025-01266-y

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 min of imaging were within 10% of the values obtained with 93 min 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 repeatability, indicating [ 11 C]PXT012253 to be a suitable PET radioligand for mGlu4.