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11C-PBR28 and 18F-PBR111 Detect White Matter Inflammatory Heterogeneity in Multiple Sclerosis.
The Journal of Nuclear Medicine ( IF 9.3 ) Pub Date : 2017-09-01 , DOI: 10.2967/jnumed.116.187161
Gourab Datta 1 , Alessandro Colasanti 1, 2 , Nicola Kalk 1 , David Owen 1 , Gregory Scott 1 , Eugenii A Rabiner 3 , Roger N Gunn 1, 3 , Anne Lingford-Hughes 1 , Omar Malik 1 , Olga Ciccarelli 4 , Richard Nicholas 1 , Lei Nei 5 , Marco Battaglini 6 , Nicola De Stefano 6 , Paul M Matthews 7
Affiliation  

The objective of this study was to assess microglial activation in lesions and in normal-appearing white matter (NAWM) of multiple sclerosis (MS) patients using PET. Methods: Thirty-four MS patients (7 with secondary progressive MS [SPMS], 27 with relapsing remitting MS [RRMS]) and 30 healthy volunteers, genetically stratified for translocator protein (TSPO) binding status, underwent PET scanning with TSPO radioligands (11C-PBR28 or 18F-PBR111). Regional TSPO availability was measured as a distribution volume ratio (DVR) relative to the caudate (a pseudoreference region). White matter lesions (WMLs) were classified as “active” (DVR highest in the lesion), “peripherally active” (perilesional DVR highest), “inactive” (DVR highest in surrounding NAWM), or “undifferentiated” (similar DVR across lesion, perilesional and NAWM volumes). Results: The mean DVR in NAWM of patients was greater than that of the healthy volunteer white matter for both radioligands. Uptake for individual WML in patients was heterogeneous, but the median WML DVR and NAWM DVR for individual patients were strongly correlated (ρ = 0.94, P = 4 × 10−11). A higher proportion of lesions were inactive in patients with SPMS (35%) than RRMS (23%), but active lesions were found in all patients, including those on highly efficacious treatments. Conclusion: TSPO radioligand uptake was increased in the brains of MS patients relative to healthy controls with 2 TSPO radiotracers. WML showed heterogeneous patterns of uptake. Active lesions were found in patients with both RRMS and SPMS. Their independent prognostic significance needs further investigation.



中文翻译:

11C-PBR28和18F-PBR111可检测多发性硬化症中的白色物质炎症异质性。

这项研究的目的是评估使用PET的多发性硬化症(MS)患者的病变和正常出现的白质(NAWM)中的小胶质细胞活化。方法:对34例MS患者(7例继发进行性MS [SPMS],27例复发缓解MS [RRMS])和30例健康志愿者进行了遗传分层,分析了转运蛋白(TSPO)的结合状态,并用TSPO放射性配体进行了PET扫描(11 C-PBR28或18F-PBR111)。区域TSPO可用性以相对于尾状部分(假参考区域)的分布体积比(DVR)进行衡量。白质病灶(WML)分为“活动”(病灶中DVR最高),“周围活动”(病灶DVR最高),“无活动”(周围NAWM中DVR最高)或“未分化”(病灶中相似的DVR) ,病灶周围和NAWM卷)。结果:两种放射配体的患者,NAWM中的平均DVR均大于健康志愿者白质。患者中单个WML的摄入量是异质的,但是单个患者的中值WML DVR和NAWM DVR是高度相关的(ρ= 0.94,P = 4×10 -11)。SPMS患者的无活动性病变比例较高(35%),高于RRMS(23%),但在所有患者中均发现有活动性病变,包括接受高效治疗的患者。结论:相对于健康对照者(使用2种TSPO放射性示踪剂),MS患者大脑中TSPO放射性配体的摄取增加。WML显示吸收的异质性模式。RRMS和SPMS患者均发现活动性病变。它们的独立预后意义需要进一步研究。

更新日期:2017-09-05
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