[C]PXT012253作为正电子发射断层扫描（PET）放射性示踪剂在健康人脑的重测特性：代谢型谷氨酸受体4（mGlu4）的PET成像

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

作者信息

Stenkrona Per, Arakawa Ryosuke, Guo Jiamei, Bang-Andersen Benny, Nag Sangram, Moein Mohammad Mahdi, Jia Zhisheng, Cselenyi Zsolt, Halldin Christer, Varrone Andrea

机构信息

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.

出版信息

EJNMMI Res. 2025 Jun 14;15(1):71. 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. [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.

RESULTS

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.

CONCLUSION

[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.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s13550-025-01266-y.

背景

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。

结果

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。