Long-term test-retest of cerebral [18F]MK-6240 binding and longitudinal evaluation of extracerebral tracer uptake in healthy controls and amnestic MCI patients,European Journal of Nuclear Medicine and Molecular Imaging

当前位置： X-MOL 学术 › Eur. J. Nucl. Med. Mol. Imaging › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Long-term test-retest of cerebral [18F]MK-6240 binding and longitudinal evaluation of extracerebral tracer uptake in healthy controls and amnestic MCI patients
European Journal of Nuclear Medicine and Molecular Imaging ( IF 9.1 ) Pub Date : 2022-07-19 , DOI: 10.1007/s00259-022-05907-5
Greet Vanderlinden ₁ , Nathalie Mertens ₁ , Laura Michiels _{2,

3,

4} , Robin Lemmens _{2,

3,

4} , Michel Koole ₁ , Mathieu Vandenbulcke _{5,

6,

7} , Koen Van Laere _{1,

7,

8}

Affiliation

Purpose

Neurofibrillary tangles (NFTs) in Alzheimer’s disease can be accurately quantified in vivo using [¹⁸F]MK-6240 PET. Short-term [¹⁸F]MK-6240 test-retest (TRT) is about 6%, but also long-term stability of cerebral uptake is of importance for longitudinal studies. Furthermore, although there is very little cerebral off-target binding, [¹⁸F]MK-6240 shows variable extracerebral uptake (ECU) assumed to represent off-target binding to leptomeningeal melanocytes. Here, we examined 6-month TRT of [¹⁸F]MK-6240 in healthy controls (HC) and investigated ECU in HC and patients with amnestic mild cognitive impairment (aMCI) with up to 2 years of follow-up. We also explored demographic factors that may be associated to ECU, including age, sex, education, smoking, and disease status.

Methods

A total cohort of 40 HC (57 ± 19 years, 21F/19 M) and 24 aMCI (72 ± 8 years, 14F/10 M) underwent baseline [¹⁸F]MK-6240 PET-MR (GE Signa), 90–120 min post injection. [¹⁸F]MK-6240 was quantified by standardized uptake value ratios (SUVR) in predefined volumes-of-interest relative to the cerebellar cortex. Ten HC (56 ± 12 years, 8F/2 M) underwent a 6-month follow-up [¹⁸F]MK-6240 to assess TRT. Also, 10 aMCI (72 ± 6 years, 5F/5 M) underwent a 2-year follow-up [¹⁸F]MK-6240 PET-MR. Longitudinal changes in ECU were assessed in both cohorts. ECU was quantified as the mean SUVR of the skull parcel (FreeSurfer 6.0) that includes the meninges.

Results

The mean gray matter [¹⁸F]MK-6240 SUVR TRT and absolute TRT in HC were 1.6 ± 3.4% and 2.4 ± 2.8%, respectively. We found no significant 6-month or 2-year differences in ECU in HC (4.4 ± 20%) and aMCI (7.9 ± 19%), respectively. In the total cohort, ECU was significantly correlated to age (r_s = − 0.48; p < 0.0001), and a multivariate analysis also showed sex differences (higher ECU in women).

Conclusion

[¹⁸F]MK-6240 shows excellent 6-month TRT, which confirms its suitability for quantification of longitudinal NFT changes. The ECU of [¹⁸F]MK-6240 is variable between subjects, influenced by age and sex, but remains stable within subjects over a 2-year time period.

中文翻译：

脑 [18F]MK-6240 结合的长期重测和健康对照和遗忘性 MCI 患者脑外示踪剂摄取的纵向评估

目的

^{使用 [ 18} F]MK-6240 PET可以在体内准确量化阿尔茨海默病中的神经原纤维缠结 (NFT) 。短期 [ ¹⁸ F]MK-6240 重测 (TRT) 约为 6%，但脑摄取的长期稳定性对于纵向研究也很重要。此外，尽管大脑脱靶结合非常少，但 [ ¹⁸ F]MK-6240 显示出可变的脑外摄取 (ECU)，假设代表与软脑膜黑素细胞的脱靶结合。^{在这里，我们检查了 [ 18}的 6 个月 TRTF]MK-6240 在健康对照组 (HC) 中，并在 HC 和遗忘性轻度认知障碍 (aMCI) 患者中调查了 ECU，并进行了长达 2 年的随访。我们还探讨了可能与 ECU 相关的人口统计因素，包括年龄、性别、教育、吸烟和疾病状况。

方法

总共 40 名 HC（57 ± 19 岁，21F/19 M）和 24 名 aMCI（72 ± 8 岁，14F/10 M）的队列接受了基线 [ ¹⁸ F]MK-6240 PET-MR（GE Signa），90–注射后 120 分钟。[ ¹⁸ F]MK-6240 通过标准化摄取值比率 (SUVR) 在相对于小脑皮层的预定义感兴趣体积中进行量化。十名 HC（56 ± 12 岁，8F/2 M）接受了为期 6 个月的随访 [ ¹⁸ F]MK-6240 以评估 TRT。此外，10 aMCI（72 ± 6 年，5F/5 M）接受了为期 2 年的随访 [ ¹⁸ F]MK-6240 PET-MR。在两个队列中评估了 ECU 的纵向变化。ECU 被量化为包括脑膜的颅骨包裹 (FreeSurfer 6.0) 的平均 SUVR。

结果

HC 中的平均灰质 [ ¹⁸ F]MK-6240 SUVR TRT 和绝对 TRT 分别为 1.6 ± 3.4% 和 2.4 ± 2.8%。我们发现 HC (4.4 ± 20%) 和 aMCI (7.9 ± 19%) 的 ECU 分别没有显着的 6 个月或 2 年差异。_{在整个队列中，ECU与}年龄显着相关（rs = − 0.48；p < 0.0001），多变量分析也显示性别差异（女性的 ECU 更高）。