Kaunzner Ulrike W, Kang Yeona, Monohan Elizabeth, Kothari Paresh J, Nealon Nancy, Perumal Jai, Vartanian Timothy, Kuceyeski Amy, Vallabhajosula Shankar, Mozley P David, Riley Claire S, Newman Stephen M, Gauthier Susan A
Judith Jaffe Multiple Sclerosis Center, Weill Cornell Medicine, 1305 York Avenue, New York City, NY, USA.
Department of Radiology/Nuclear Medicine, Weill Cornell Medicine, New York, 516 E 72nd St, New York City, NY, USA.
Mult Scler Relat Disord. 2017 Jul;15:27-33. doi: 10.1016/j.msard.2017.04.008. Epub 2017 Apr 29.
The objective of this study is to longitudinally analyze the uptake of [C]PK11195-PET in multiple sclerosis patients after 3 and 6 months of natalizumab treatment.
Eighteen MS patients, starting treatment with monocloncal anti-VLA-4, were enrolled in a longitudinal PK-PET study. PK uptake was quantified by volume of distribution (VT) calculation using image-derived input function at baseline, 3 and 6 months. Pharmacokinetic quantification was done using a segmented MRI, and selected areas included white matter, gadolinium enhancing lesions, non-enhancing lesions, cortical grey matter and thalamus. VTs of lesions were calculated in reference to each patient's white matter (VT ratio=VTr), to consider physiologic variability.
Test-retest variability was stable for healthy control (HC). Quantification of PK uptake was completed in 18 patients, and baseline uptake was compared to 6-month uptake. After the start of natalizumab VTr significantly decreased in 13 individual enhancing lesions present within 5 patients (p=0.001). Moreover, VTr of the sum of non-enhancing lesions showed a moderate decrease (p=0.03). No longitudinal changes were detected in normal appearing white matter, the thalamus and cortical grey matter.
A reduction in PK11195 uptake was observed in both enhancing and chronic lesions after the start of natalizumab. PK11195 PET can be used as tool to assess the longitudinal change in MS lesions.
本研究的目的是纵向分析那他珠单抗治疗3个月和6个月后多发性硬化症患者对[C]PK11195-PET的摄取情况。
18例开始使用单克隆抗VLA-4治疗的多发性硬化症患者纳入一项纵向PK-PET研究。在基线、3个月和6个月时，使用图像衍生输入函数通过分布容积（VT）计算对PK摄取进行定量。使用分段MRI进行药代动力学定量，选定区域包括白质、钆增强病变、非增强病变、皮质灰质和丘脑。根据每位患者的白质计算病变的VT（VT比率=VTr），以考虑生理变异性。
健康对照（HC）的重测变异性稳定。18例患者完成了PK摄取定量，并将基线摄取与6个月时的摄取进行比较。那他珠单抗开始治疗后，5例患者体内存在的13个单个增强病变的VTr显著降低（p=0.001）。此外，非增强病变总和的VTr有中度降低（p=0.03）。在正常外观的白质、丘脑和皮质灰质中未检测到纵向变化。
那他珠单抗开始治疗后，在增强病变和慢性病变中均观察到PK11195摄取减少。PK11195 PET可作为评估多发性硬化症病变纵向变化的工具。
