Cited by 107Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchMedical Imaging Techniques and Applications

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Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles

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Lohith, Talakad G., Bennacef, Idriss, Vandenberghe, Rik, Vandenbulcke, Mathieu, Salinas, Cristian A., Declercq, Ruben, Reynders, Tom, Telan-Choing, N. Florestina, Riffel, Kerry, Celen, Sofie, Serdons, Kim, Bormans, Guy, Tsai, Kuenhi, Walji, Abbas, Hostetler, Eric D., Evelhoch, Jeffrey L., Van Laere, Koen, Forman, Mark, Stoch, Aubrey, Sur, Cyrille, Struyk, Arie·2019·Journal of Nuclear Medicine

DOI 10.2967/jnumed.118.208215

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Abstract

18F-MK-6240 (18F-labeled 6-(fluoro)-3-(1H-pyrrolo[2,3-c]pyridin-1-yl)isoquinolin-5-amine) is a highly selective, subnanomolar-affinity PET tracer for imaging neurofibrillary tangles (NFTs). Plasma kinetics, brain uptake, and preliminary quantitative analysis of 18F-MK-6240 in healthy elderly (HE) subjects, subjects with clinically probable Alzheimer disease (AD), and subjects with amnestic mild cognitive impairment were characterized in a study that is, to our knowledge, the first to be performed on humans. Methods: Dynamic PET scans of up to 150 min were performed on 4 cognitively normal HE subjects, 4 AD subjects, and 2 amnestic mild cognitive impairment subjects after a bolus injection of 152–169 MBq of 18F-MK-6240 to evaluate tracer kinetics and distribution in brain. Regional SUV ratio (SUVR) and distribution volume ratio were determined using the cerebellar cortex as a reference region. Total distribution volume was assessed by compartmental modeling using radiometabolite-corrected input function in a subgroup of 6 subjects. Results:18F-MK-6240 had rapid brain uptake with a peak SUV of 3–5, followed by a uniformly quick washout from all brain regions in HE subjects; slower clearance was observed in regions commonly associated with NFT deposition in AD subjects. In AD subjects, SUVR between 60 and 90 min after injection was high (approximately 2–4) in regions associated with NFT deposition, whereas in HE subjects, SUVR was approximately 1 across all brain regions, suggesting high tracer selectivity for binding NFTs in vivo. 18F-MK-6240 total distribution volume was approximately 2- to 3-fold higher in neocortical and medial temporal brain regions of AD subjects than in HE subjects and stabilized by 60 min in both groups. Distribution volume ratio estimated by the Logan reference tissue model or compartmental modeling correlated well (R2 > 0.9) to SUVR from 60 to 90 min for AD subjects. Conclusion:18F-MK-6240 exhibited favorable kinetics and high binding levels to brain regions with a plausible pattern for NFT deposition in AD subjects. In comparison, negligible tracer binding was observed in HE subjects. This pilot study suggests that simplified ratio methods such as SUVR can be used to quantify NFT binding. These results support further clinical development of 18F-MK-6240 for potential application in longitudinal studies.

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Additional file 1 of A dual-time-window protocol to reduce acquisition time of dynamic tau PET imaging using [18F]MK-6240
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Authors: Lohith, T. G., Bennacef, I., Vandenberghe, R., Vandenbulcke, M., Salinas, C. A., Declercq, R., Reynders, T., Telan-Choing, N. F., Riffel, K., Celen, S., Serdons, K., Bormans, G., Tsai, K., Walji, A., Hostetler, E. D., Evelhoch, J. L., Van Laere, K., Forman, M., Stoch, A., Sur, C., & Struyk, A.
Affiliations: Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
Universitair Ziekenhuis Leuven (BE)
MSD (Belgium) (BE)
KU Leuven (BE)
ORCID: Lohith, Talakad G.
Bennacef, Idriss
Vandenberghe, Rik
Vandenbulcke, Mathieu
Reynders, Tom
Celen, Sofie
Serdons, Kim
Bormans, Guy
Stoch, Aubrey
Struyk, Arie
Venue: Journal of Nuclear Medicine
Publisher: Society of Nuclear Medicine
Published: 2018-06-07
Volume: 60
Issue: 1
Pages: 107-114
ISSN: 0161-5505 (ISSN-L)
2159-662X
DOI: 10.2967/jnumed.118.208215
OpenAlex: W2806931468
Cited by: 107
References: 23
Citations by year: 2026: 6 · 2025: 8 · 2024: 5 · 2023: 12 · 2022: 15 · 2021: 25 · 2020: 14 · 2019: 19 · 2018: 3
FWCI: 10.46
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Nuclear Medicine (publishedVersion)
PubMed (publishedVersion)
Lirias (submittedVersion, other-oa)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords: [18F]MK-6240, neurofibrillary tangles, Alzheimer's disease, amnestic mild cognitive impairment, PET radiotracer, tracer kinetics, volume of distribution, compartmental modeling, medial temporal lobe, cerebellar cortex
MeSH terms: Aged, Aged, 80 and over, Alzheimer Disease, Brain, Female, Fluorine Radioisotopes, Humans, Isoquinolines, Kinetics, Magnetic Resonance Imaging, Male, Middle Aged, Pilot Projects, Radioactive Tracers, Case-Control Studies, Neurofibrillary Tangles, Positron-Emission Tomography

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Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles

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