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European Journal of Nuclear Medicine and Molecular Imaging
Published in: European Journal of Nuclear Medicine and Molecular Imaging 13/2022

19-07-2022 | Mild Cognitive Impairment | Original Article

Long-term test-retest of cerebral [18F]MK-6240 binding and longitudinal evaluation of extracerebral tracer uptake in healthy controls and amnestic MCI patients

Authors: Greet Vanderlinden, Nathalie Mertens, Laura Michiels, Robin Lemmens, Michel Koole, Mathieu Vandenbulcke, Koen Van Laere

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 13/2022

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Abstract

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 (rs =  − 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.
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Metadata
Title
Long-term test-retest of cerebral [18F]MK-6240 binding and longitudinal evaluation of extracerebral tracer uptake in healthy controls and amnestic MCI patients
Authors
Greet Vanderlinden
Nathalie Mertens
Laura Michiels
Robin Lemmens
Michel Koole
Mathieu Vandenbulcke
Koen Van Laere
Publication date
19-07-2022
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 13/2022
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-022-05907-5

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