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57/100

✓ Peer-reviewed alzhub usefulness score 57 out of 100. Brain scans and imaging

Topic: Plasma and spinal-fluid biomarkers

Plain-language summary

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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APA 7th

Lohith, T. G., Bennacef, I., Vandenberghe, R. R., Vandenbulcke, M., Salinas, C. A., Declercq, R., et al. (2018). Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles. Journal of Nuclear Medicine. https://doi.org/10.2967/jnumed.118.208215

Vancouver

Lohith TG, Bennacef I, Vandenberghe RR, Vandenbulcke M, Salinas CA, Declercq R, et al. Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles. Journal of Nuclear Medicine. 2018. doi:10.2967/jnumed.118.208215. PMID: 29880509.

BibTeX

@article{lohith2018-29880509,
  author  = {Lohith, Talakad Goolaiah and Bennacef, Idriss and Vandenberghe, Rik R. and Vandenbulcke, Mathieu and Salinas, Cristian A and Declercq, Ruben and Reynders, Tom and Telan-Choing, N. Florestina and others},
  title   = {{Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles}},
  journal = {Journal of Nuclear Medicine},
  year    = {2018},
  doi     = {10.2967/jnumed.118.208215},
  pmid    = {29880509},
  url     = {https://doi.org/10.2967/jnumed.118.208215}
}

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How to read this study

Design: this is a follow-up (cohort) study. People are observed over time and not assigned to anything, so an association can reflect other differences between groups. Look at how long follow-up lasted, how many dropped out, and whether the authors adjusted for age, education and other health conditions.
Size: the record gives no participant count. Look for one in the original before trusting a pattern.
Effect: the record gives no effect size, so the summary above cannot say how large any difference was.

What the evidence grade means here

This page is graded moderate. alzhub.org assigns the grade automatically from keywords in the abstract, not from reading the paper. Moderate means the abstract mentions a cohort, case-control or longitudinal design. It can add at most 5 of the 100 points in the study score, and it is a label about design, not a verdict on whether the findings are true.

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Key findings

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.
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.

New to this subject? Start with our plain-English guide: Brain scans & tests →

Study details

Study designlongitudinal study
Evidence strengthModerate

How this study scored 57/100

Published in a peer-reviewed journal, and it is a longitudinal study following the same people over time. Scored zero for sample size, effect reported, studied in people and randomized / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multicenter collaboration, so those were left out: it earned 33 of the 58 points we could judge it on, which is 57 out of 100.

Component	Points	Why
Journal tier	7 / 10	Tier 3 — peer-reviewed journal (Journal of Nuclear Medicine)
Journal's citation record	— / 4	No journal record from OpenAlex — left out of this score
Study design	7 / 12	A longitudinal study following the same people over time
Strength of evidence	3 / 5	Rated “moderate” in our summary
Peer-review validation	10 / 10	Peer-reviewed. Published as an article in a named peer-reviewed journal.
How recent	2 / 5	2018 — within 10 year(s) of the newest study here
Sample size	0 / 4	Participant count not stated — scores zero (not stated in the record — scored 0)
Effect reported	0 / 3	No effect size reported — scores zero (not stated in the record — scored 0)
Studied in people	0 / 3	Not stated whether this was studied in people — scores zero (not stated in the record — scored 0)
Randomized / blinded	0 / 2	No randomization or blinding stated — scores zero (not stated in the record — scored 0)
Times cited	— / 7	No citation count (not found in OpenAlex) — left out of this score
Citations per year	— / 5	No citation count or no year — left out of this score
Impact for its field and year	— / 6	No field-weighted citation impact (OpenAlex has none yet) — left out of this score
Cited by studies here	— / 6	Not yet checked against this library's citation graph — left out of this score
Still being cited	— / 4	No yearly citation counts — left out of this score
Senior author's track record	— / 4	Senior author's record not available — left out of this score
Institution's track record	— / 3	No institution listed in OpenAlex — left out of this score
Multicenter collaboration	— / 3	Institutions not listed — left out of this score
Indexed in PubMed	2 / 2	Indexed in PubMed (PMID 29880509)
Free to read	2 / 2	Free to read
Points	33 / 58	Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 33 of the 58 points we could judge it on is 57 out of 100.
Total	57 / 100	—

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