The Journal of Nuclear Medicine ( IF 9.1 ) Pub Date : 2025-01-02 , DOI: 10.2967/jnumed.124.268233 Minyoung Oh, Joachim Brumberg, Vesna Sossi, Andrea Varrone
Serotonin transporter (SERT) availability was assessed using 2 tracers, [11C]N,N-dimethyl-2-(2-amino-4-cyanophenylthio)benzylamine ([11C]DASB) and [11C]N,N-dimethyl-2-(2-amino-4-fluoromethylphenylthio)benzylamine) ([11C]MADAM), in independent cohorts of patients and controls. This study aimed to independently confirm whether SERT remains intact in nondepressed individuals with early-stage Parkinson disease (PD), because the use of diverse methodologies could potentially yield disparate results. Methods: Seventeen PD patients (5 women and 12 men; age, 64 ± 7 y; Unified Parkinson’s Disease Rating Scale motor score, 23 ± 5; Beck Depression Inventory score, 5 ± 4) and 20 age- and sex-matched healthy controls underwent [11C]MADAM PET at Karolinska Institutet. Fifteen PD patients (5 women and 10 men; age, 59 ± 9 y; Unified Parkinson’s Disease Rating Scale motor score, 15 ± 7; Beck Depression Inventory score, 4 ± 4) and 8 controls were examined with [11C]DASB PET at the University of British Columbia. PET scans were performed at both institutions using a high-resolution research tomograph. A simplified reference tissue model and Logan graphical analysis were used to calculate the regional nondisplaceable binding potential (BPND), using the cerebellum as the reference. Parametric BPND images were generated using wavelet-aided parametric imaging. MRI-defined volumes of interest included cortical and subcortical regions, as well as brain stem nuclei. Results: There were no significant differences between controls and early-stage PD patients in either the [11C]DASB or the [11C]MADAM cohort, regardless of the analysis method. Group differences (Cohen d) in the [11C]DASB cohort ranged from 0.34 to 0.86 in brain stem nuclei, 0.09 to 0.61 in subcortical regions, and 0.28 to 0.70 in cortical regions. In the [11C]MADAM cohort, they ranged from 0.16 to 0.40, 0.19 to 0.55, and 0.32 to 0.61, respectively. Logan BPND highly correlated with simplified reference tissue model BPND for both tracers in each group (P < 0.001). Conclusion: SERT availability is relatively preserved in nondepressed patients with PD. This study suggests that serotonergic degeneration is not a major feature of the disease in nondepressed patients with nonadvanced disease.
中文翻译:
使用 [11C]MADAM 或 [11C]DASB 测量帕金森病中保留的血清素转运蛋白可用性:一项包括 2 个独立的非抑郁患者队列的研究
使用 2 种示踪剂 [11C]N,N-二甲基-2-(2-氨基-4-氰基苯基硫基)苄胺 ([11C]DASB) 和 [11C]N,N-二甲基-2-(2-氨基-4-氟甲基苯硫基)苄胺) ([11C]MADAM) 评估血清素转运蛋白 (SERT) 的可用性,在患者和对照的独立队列中。本研究旨在独立确认早期帕金森病 (PD) 非抑郁个体的 SERT 是否保持完整,因为使用不同的方法可能会产生不同的结果。方法:17 名 PD 患者 (5 名女性和 12 名男性;年龄 64 ± 7 岁;统一帕金森病评定量表运动评分,23 ± 5;贝克抑郁量表评分,5 ± 4) 和 20 名年龄和性别匹配的健康对照在卡罗林斯卡医学院接受了 [11C]MADAM PET。15 名 PD 患者 (5 名女性和 10 名男性;年龄 59 ± 9 岁;统一帕金森病评定量表运动评分,15 ± 7;在不列颠哥伦比亚大学用 [11C]DASB PET 检查了贝克抑郁量表评分 4 ± 4) 和 8 个对照。在两个机构都使用高分辨率研究断层扫描进行 PET 扫描。使用简化的参考组织模型和 Logan 图形分析来计算区域不可置换结合电位 (BPND),以小脑为参考。使用小波辅助参数成像生成参数 BPND 图像。MRI 定义的感兴趣体积包括皮质和皮质下区域,以及脑干核。 结果:无论分析方法如何,在 [11C]DASB 或 [11C]MADAM 队列中,对照组和早期 PD 患者之间均无显著差异。[11C]DASB 队列中的组差异 (Cohen d) 范围为脑干核 0.34 至 0.86、皮质下区域 0.09 至 0.61 和皮质区域 0.28 至 0.70。在 [11C] MADAM 队列中,它们的范围分别为 0.16 至 0.40、0.19 至 0.55 和 0.32 至 0.61。每组中两种示踪剂的 Logan BPND 与简化的参考组织模型 BPND 高度相关 (P < 0.001)。结论:SERT 可用性在非抑郁 PD 患者中相对保留。这项研究表明,5-羟色胺能变性并不是非晚期疾病非抑郁患者的主要特征。