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Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection
Milos D Ikonomovic, Chris J Buckley, Kerstin Heurling, Paul Sherwin, Paul A Jones, Michelle Zanette, Chester A Mathis, William E Klunk et al.. Acta neuropathologica communications, 2016-12-12
Topic: Plasma and spinal-fluid biomarkers
In vivo imaging of fibrillar β-amyloid deposits may assist clinical diagnosis of Alzheimer's disease (AD), aid treatment selection for patients, assist clinical trials of therapeutic drugs through subject selection, and be used as an outcome measure. A recent phase III trial of [18F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology. Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups. The GE067-026 trial demonstrated 91% sensitivity and 90% specificity of [18F]flutemetamol PET by majority read for the presence of moderate or frequent plaques. The probability of an abnormal [18F]flutemetamol scan increased with neocortical plaque density and AD diagnosis. All dementia cases with non-AD neurodegenerative diseases and those without histopathological features of β-amyloid deposits were [18F]flutemetamol negative. Majority PET assessments accurately reflected the amyloid plaque burden in 90% of cases. However, ten cases demonstrated a mismatch between PET image interpretations and post-mortem findings. Although tracer retention was best associated with amyloid in neuritic plaques, amyloid in diffuse plaques and cerebral amyloid angiopathy best explain three [18F]flutemetamol positive cases with mismatched (sparse) neuritic plaque burden. Advanced cortical atrophy was associated with the seven false negative [18F]flutemetamol images. The interpretation of images from pathologically equivocal cases was associated with low reader confidence and inter-reader agreement. Our results support that amyloid in neuritic plaque burden is the primary form of β-amyloid pathology detectable with [18F]flutemetamol PET imaging. ClinicalTrials.gov NCT01165554. Registered June 21, 2010; NCT02090855. Registered March 11, 2014.
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APA 7th
Ikonomovic, M. D., Buckley, C. J., Heurling, K., Sherwin, P., Jones, P. A., Zanette, M., et al. (2016). Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection. Acta neuropathologica communications. https://doi.org/10.1186/s40478-016-0399-z
Vancouver
Ikonomovic MD, Buckley CJ, Heurling K, Sherwin P, Jones PA, Zanette M, et al. Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection. Acta neuropathologica communications. 2016. doi:10.1186/s40478-016-0399-z. PMID: 27955679.
BibTeX
@article{ikonomovic2016-27955679,
author = {Ikonomovic, Milos D and Buckley, Chris J and Heurling, Kerstin and Sherwin, Paul and Jones, Paul A and Zanette, Michelle and Mathis, Chester A and Klunk, William E and others},
title = {{Post-mortem histopathology underlying β-amyloid PET imaging following flutemetamol F 18 injection}},
journal = {Acta neuropathologica communications},
year = {2016},
doi = {10.1186/s40478-016-0399-z},
pmid = {27955679},
url = {https://doi.org/10.1186/s40478-016-0399-z}
}
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Key findings
- A recent phase III trial of [18F]flutemetamol positron emission tomography (PET) imaging in 106 end-of-life subjects demonstrated the ability to identify fibrillar β-amyloid by comparing in vivo PET to post-mortem histopathology.
- Post-mortem analyses demonstrated a broad and continuous spectrum of β-amyloid pathology in AD and other dementing and non-dementing disease groups.
- The GE067-026 trial demonstrated 91% sensitivity and 90% specificity of [18F]flutemetamol PET by majority read for the presence of moderate or frequent plaques.
- However, ten cases demonstrated a mismatch between PET image interpretations and post-mortem findings.
- Although tracer retention was best associated with amyloid in neuritic plaques, amyloid in diffuse plaques and cerebral amyloid angiopathy best explain three [18F]flutemetamol positive cases with mismatched (sparse) neuritic plaque burden.
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Study details
- Evidence strengthLow
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported and randomised / 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 free to read, so those were left out: it earned 26 of the 59 points we could judge it on, which is 44 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Acta neuropathologica communications) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2016 — within 20 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 | 3 / 3 | Studied in people (pubmed indexes it as a clinical or observational study) |
| Randomised / blinded | 0 / 2 | No randomisation 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 |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 27955679) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 26 / 59 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 59 points we could judge it on is 44 out of 100. |
| Total | 44 / 100 | — |
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