The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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 the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0127-z · Cited by 3,172
Staging of alzheimer's disease-related neurofibrillary changes
Braak, H., & Braak, E. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)00021-6 · Cited by 2,357
A New Rating Scale for Age-Related White Matter Changes Applicable to MRI and CT
Wahlund, L., Barkhof, F., Fazekas, F., Bronge, L., Augustin, M., Sjögren, M., Wallin, A., Adèr, H., Leys, D., Pantoni, L., et al. (2001) · Stroke · doi:10.1161/01.str.32.6.1318 · Cited by 1,838
Distribution Volume Ratios without Blood Sampling from Graphical Analysis of PET Data
Logan, J., Fowler, J. S., Volkow, N. D., Wang, G., Ding, Y., & Alexoff, D. L. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199609000-00008 · Cited by 1,515
Hammers, A., Allom, R. J., Koepp, M. J., Free, S. L., Myers, R., Lemieux, L., Mitchell, T. N., Brooks, D. J., & Duncan, J. S. (2003) · Human Brain Mapping · doi:10.1002/hbm.10123 · Cited by 1,270
Early Clinical PET Imaging Results with the Novel PHF-Tau Radioligand [F18]-T808
Chien, D. T., Szardenings, A. K., Bahri, S., Walsh, J. C., Mu, F., Xia, C. A., Shankle, W. R., Lerner, A. J., Su, M., Elizarov, A. M., et al. (2013) · Journal of Alzheimer s Disease · doi:10.3233/jad-130098 · Cited by 683
Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807
Chien, D. T., Bahri, S., Szardenings, A. K., Walsh, J. C., Mu, F., Su, M.-Y., Shankle, W. R., Elizarov, A., & Kolb, H. C. (2013) · Journal of Alzheimer's Disease · doi:10.3233/jad-122059 · Cited by 651 · cited 1×
“Cerebellar gray matter has been reported as devoid of NFT deposition, and therefore, similar to the evaluation of other tau PET tracers, we used the cerebellar cortex as the reference region (11,12).”
ResultMarquié, M., Normandin, M. D., Vanderburg, C. R., Costantino, I. M., Bien, E. A., Rycyna, L. G., Klunk, W. E., Mathis, C. A., Ikonomovic, M. D., Debnath, M. L., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24517 · Cited by 615
Tau imaging: early progress and future directions
Villemagne, V. L., Fodero-Tavoletti, M. T., Masters, C. L., & Rowe, C. C. (2015) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70252-2 · Cited by 501
Monoamine oxidase B inhibitor, selegiline, reduces 18F-THK5351 uptake in the human brain
Ng, K. P., Pascoal, T. A., Mathotaarachchi, S. S., Therriault, J., Kang, M. S., Shin, M., Guiot, M.-C., Guo, Q., Harada, R., Comley, R. A., et al. (2017) · Alzheimer s Research & Therapy · doi:10.1186/s13195-017-0253-y · Cited by 351
Cited by
Sorted by citations
Items 101–107 of 107
Kolinger, G. D., García, D. V., Lohith, T. G., Hostetler, E. D., Sur, C., Struyk, A. F., Boellaard, R., & Koole, M. (2021) · Figshare · doi:10.6084/m9.figshare.14691939
Self-citationKolinger, G. D., García, D. V., Lohith, T. G., Hostetler, E. D., Sur, C., Struyk, A. F., Boellaard, R., & Koole, M. (2021) · Figshare · doi:10.6084/m9.figshare.14691942
Self-citationMatsuda, H. (2026) · Springer eBooks · doi:10.1007/978-981-95-5222-1_3
Structured reading for Tau PET Imaging in Alzheimer's disease and related dementias
Orunmuyi, A. T., Wang, M., Rogeau, A., Dickson, J. C., Groves, A. M., Bomanji, J. B., Fraioli, F., & Weil, R. S. (2026) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2026.02.005
The importance of tau tracers in the diagnosis of neurodegenerative diseases
Sadeghian, S., & Seradj, S. H. (2026) · Results in Chemistry · doi:10.1016/j.rechem.2026.103531
Hu, T.-W., Prince, J., Zhou, L., Wang, X. H., Tanzi, E. B., Khalafi, M., Nehmeh, S. A., Pahlajani, S. S., Hojjati, S. H., Glodzik, L., et al. (2026) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-026-07976-2
Liao, K., Li, J., Jiao, F., Zhang, Z., Xu, L., Wang, Z., Li, W., & Pang, H. (2026) · EJNMMI Physics · doi:10.1186/s40658-026-00914-z
Metadata
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
