Delva Aline, Koole Michel, Serdons Kim, Bormans Guy, Skinbjerg Mette, Khetarpal Vinod, Liu Longbin, Bard Jonathan, Doot Robert, Warner John H, Sathe Swati, Sampaio Cristina, Wood Andrew, Van Laere Koen, Vandenberghe Wim
Department of Neurosciences, KU Leuven, Leuven, Belgium.
Department of Neurology, University Hospitals Leuven, Leuven, Belgium.
Eur J Nucl Med Mol Imaging. 2025 Jun 18. doi: 10.1007/s00259-025-07394-w.
[C]CHDI-00485180-R ([C]CHDI-180R) is a novel PET radioligand developed to image aggregated mutant huntingtin (mHTT). Data from mouse models of Huntington's disease (HD) and biodistribution studies in healthy volunteers suggested that [C]CHDI-180R is a promising candidate for in vivo determination of cerebral aggregated mHTT levels using PET. In the iMagemHTT study reported here, we investigated [C]CHDI-180R kinetic properties and suitability to quantify aggregated mHTT in brains of people with HD (pwHD).
A total of 12 pwHD (53.7 ± 6.9y, 5 M/ 7 F, Shoulson-Fahn stage 2) and 12 healthy controls (HC; six young [26.8 ± 3.2y], 2 M/ 4 F; six age-matched [53.7 ± 6.1y],2 M/ 4 F) were included. We conducted dynamic 90 min [C]CHDI-180R PET imaging with arterial sampling and radiometabolite quantification, and delineated volumes of interest (VOIs) using individual 3D T1-MRI. We calculated total distribution volumes (V) using 2-compartment modelling (2TCM) as well as Logan graphical analysis and determined distribution volume ratios relative to cerebellum (DVR). We applied partial volume correction, and assessed test-retest variability in pwHD.
V showed considerable intersubject variability among HC (V = 0.68 ± 0.22) and pwHD (V = 0.75 ± 0.26), without any regional significant differences between the groups. V test-retest variability was high if test and retest scans were performed on the same day, but low (< 10%) if performed one week apart. DVR showed significantly higher [C]CHDI-180R relative binding in frontal, temporal, parietal, occipital and composite cortex VOIs (average increase 19.5 ± 6.1%) in pwHD than age-matched HC.
[C]CHDI-180R V showed high intersubject variability and relatively low signal-to-background ratio. However, significant differences were found between pwHD and HC using cerebellum as pseudo-reference region.
EudraCT 2018-001862-41 clinicaltrials.gov NCT03810898 https://clinicaltrials.gov/study/NCT03810898?term=NCT03810898&rank=1.
[C]CHDI - 00485180 - R（[C]CHDI - 180R）是一种新型正电子发射断层显像（PET）放射性配体，用于对聚集的突变型亨廷顿蛋白（mHTT）进行成像。来自亨廷顿舞蹈病（HD）小鼠模型的数据以及健康志愿者的生物分布研究表明，[C]CHDI - 180R是使用PET在体内测定大脑中聚集的mHTT水平的一个有前景的候选物。在本文报道的iMagemHTT研究中，我们研究了[C]CHDI - 180R的动力学特性以及在HD患者（pwHD）大脑中量化聚集的mHTT的适用性。
共纳入12例pwHD（年龄53.7±6.9岁，5例男性/7例女性，Shoulson - Fahn分期2期）和12名健康对照者（HC；6名年轻人[26.8±3.2岁]，2例男性/4例女性；6名年龄匹配者[53.7±6.1岁]，2例男性/4例女性）。我们进行了90分钟的动态[C]CHDI - 180R PET成像，同时进行动脉采样和放射性代谢物定量分析，并使用个体三维T1加权磁共振成像（MRI）勾勒感兴趣区（VOI）。我们使用双室模型（2TCM）以及Logan图形分析计算总分布容积（V），并确定相对于小脑的分布容积比（DVR）。我们应用了部分容积校正，并评估了pwHD的重测变异性。
V在HC组（V = 0.68±0.22）和pwHD组（V = 0.75±0.26）中显示出相当大的个体间变异性，两组之间无任何区域显著差异。如果在同一天进行测试和重测扫描，V的重测变异性较高，但如果间隔一周进行，则变异性较低（<10%）。与年龄匹配的HC相比，pwHD的额叶、颞叶、顶叶、枕叶和复合皮质VOI中DVR显示[C]CHDI - 180R相对结合显著更高（平均增加19.5±6.1%）。
[C]CHDI - 180R的V显示出较高的个体间变异性和相对较低的信噪比。然而，以小脑作为伪参考区域时，pwHD和HC之间发现了显著差异。
欧洲临床试验数据库（EudraCT）2018 - 001862 - 41 美国国立医学图书馆临床试验注册中心（clinicaltrials.gov）NCT编号NCT03810898 网址：https://clinicaltrials.gov/study/NCT03810898?term=NCT03810898&rank=1
