Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles
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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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18F-MK-6240 exhibits regional retention in a plausible pattern for NFT pathology in AD.
“They found that 18F-MK-6240 exhibits regional retention in a plausible pattern for NFT pathology in AD.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [81]
In NFT depositing regions, signal magnitude (SUVR or VT) was higher in AD/MCI subjects compared with healthy elderly subjects, with no evidence of off-target binding in healthy elderly subjects.
“Importantly, in NFT depositing regions, signal magnitude in terms of semi quantitative SUVR or fully quantitative VT values were higher in AD/MCI subjects compared with HE subjects, with no evidence of off-target binding in HE subjects [81].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [81]
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Self-citation
- 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
- 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
- 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
- Health Sciences › Medicine › Physiology › 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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