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

Autor: Vanderlinden G; Nuclear Medicine and Molecular Imaging, Imaging and Pathology, KU Leuven, Leuven, Belgium. greet.vanderlinden@kuleuven.be., Mertens N; Nuclear Medicine and Molecular Imaging, Imaging and Pathology, KU Leuven, Leuven, Belgium., Michiels L; Department of Neurology, University Hospitals UZ Leuven, Leuven, Belgium.; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.; Department of Neurosciences, KU Leuven, Leuven, Belgium., Lemmens R; Department of Neurology, University Hospitals UZ Leuven, Leuven, Belgium.; VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.; Department of Neurosciences, KU Leuven, Leuven, Belgium., Koole M; Nuclear Medicine and Molecular Imaging, Imaging and Pathology, KU Leuven, Leuven, Belgium., Vandenbulcke M; Research Group Psychiatry, KU Leuven, Leuven, Belgium.; Department of Old-Age Psychiatry, University Hospitals UZ Leuven, Leuven, Belgium.; Leuven Brain Institute, Leuven, Belgium., Van Laere K; Nuclear Medicine and Molecular Imaging, Imaging and Pathology, KU Leuven, Leuven, Belgium.; Leuven Brain Institute, Leuven, Belgium.; Department of Nuclear Medicine, University Hospitals UZ Leuven, Leuven, Belgium.
Jazyk: angličtina
Zdroj: European journal of nuclear medicine and molecular imaging [Eur J Nucl Med Mol Imaging] 2022 Nov; Vol. 49 (13), pp. 4580-4588. Date of Electronic Publication: 2022 Jul 19.
DOI: 10.1007/s00259-022-05907-5
Abstrakt: Purpose: Neurofibrillary tangles (NFTs) in Alzheimer's disease can be accurately quantified in vivo using [ 18 F]MK-6240 PET. Short-term [ 18 F]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, [ 18 F]MK-6240 shows variable extracerebral uptake (ECU) assumed to represent off-target binding to leptomeningeal melanocytes. Here, we examined 6-month TRT of [ 18 F]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 [ 18 F]MK-6240 PET-MR (GE Signa), 90-120 min post injection. [ 18 F]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 [ 18 F]MK-6240 to assess TRT. Also, 10 aMCI (72 ± 6 years, 5F/5 M) underwent a 2-year follow-up [ 18 F]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 [ 18 F]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: [ 18 F]MK-6240 shows excellent 6-month TRT, which confirms its suitability for quantification of longitudinal NFT changes. The ECU of [ 18 F]MK-6240 is variable between subjects, influenced by age and sex, but remains stable within subjects over a 2-year time period.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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