Stenkrona Per, Arakawa Ryosuke, Guo Jiamei, Bang-Andersen Benny, Nag Sangram, Moein Mohammad Mahdi, Jia Zhisheng, Cselenyi Zsolt, Halldin Christer, Varrone Andrea
Department of Clinical Neuroscience, Karolinska Institutet and Centre for Psychiatry Research, Stockholm County Council, Stockholm, S-17176, Sweden.
Department of Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P. R. China.
EJNMMI Res. 2025 Jun 14;15(1):71. doi: 10.1186/s13550-025-01266-y.
The metabotropic glutamate receptor 4 (mGlu4) has been proposed as a target for Parkinson’s disease to measure levodopa-induced dyskinesia. [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 [C]PXT012253 in healthy volunteers.
Six subjects (4 females) completed. [C]PXT012253 displayed high uptake and rapid wash-out. Unchanged [C]PXT012253 at 20 min was 10–20%. in subcortical regions was higher than in cortical regions. 2TC provided better fits than 1TC. 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 <7% and ICC > 0.93 using the 2TC, Logan and MA1 graphical analyses. Time stability analysis showed that values estimated using 63 min of imaging were within 10% of the values obtained with 93 min with all three models.
[C]PXT012253 showed a high brain uptake, with rapid washout and metabolism. was reliably estimated using 2TC, Logan GA and MA1. The test-retest metrics showed high repeatability, indicating [C]PXT012253 to be a suitable PET radioligand for mGlu4.
The online version contains supplementary material available at 10.1186/s13550-025-01266-y.
代谢型谷氨酸受体4（mGlu4）已被提议作为帕金森病中衡量左旋多巴诱导的异动症的一个靶点。[C]PXT012253是一种用于mGlu4的正电子发射断层扫描（PET）放射性配体（亲和力为3.4 nM），此前已在非人类灵长类动物中进行了表征。我们旨在确定健康志愿者中[C]PXT012253结合参数的最佳定量方法、采集持续时间以及重测信度。
6名受试者（4名女性）完成了研究。[C]PXT012253表现出高摄取和快速清除。20分钟时未改变的[C]PXT012253为10%-20%。皮层下区域的摄取高于皮层区域。双组织隔室（2TC）模型比单组织隔室（1TC）模型拟合效果更好。通过Logan广义动脉输入函数（GA）和MA1分析得到的结果与2TC-约束模型（CM）相关。MA1分析比Logan分析具有更好的可识别性和更低的标准误差。使用2TC、Logan和MA1图形分析，脑桥、壳核和丘脑的重测指标显示绝对变异性<7%，组内相关系数（ICC）>0.93。时间稳定性分析表明，使用63分钟成像估计的参数值与使用93分钟成像得到的值在所有三种模型中均在10%以内。
[C]PXT012253显示出高脑摄取，具有快速清除和代谢的特点。使用2TC、Logan GA和MA1可以可靠地估计结合参数。重测指标显示出高重复性，表明[C]PXT012253是一种适用于mGlu4的PET放射性配体。
在线版本包含可在10.1186/s13550-025-01266-y获取的补充材料。
