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Record W4408300332 · doi:10.1021/acschemneuro.4c00866

Radiosynthesis, <i>In Vitro</i> Characterization, and <i>In Vivo</i> PET Neuroimaging of [<sup>18</sup>F]F-4 for Tau Protein: A First-in-Human PET Study

2025· article· en· W4408300332 on OpenAlexafffund
Anton Lindberg, Junchao Tong, Chao Zheng, André Mueller, Heiko Kroth, Andrew Stephens, Chester A. Mathis, Neil Vasdev

Bibliographic record

VenueACS Chemical Neuroscience · 2025
Typearticle
Languageen
FieldMedicine
TopicAlzheimer's disease research and treatments
Canadian institutionsUniversity of Toronto
FundersNational Institute on AgingTau ConsortiumCanada Research ChairsCanada Foundation for InnovationOntario Research FoundationAzrieli FoundationMichael J. Fox Foundation for Parkinson's Research
KeywordsPositron emission tomographyProgressive supranuclear palsyRadiosynthesisIn vivoNeuroimagingCorticobasal degenerationMolecular imagingPet imagingPreclinical imagingHuman brainBlood–brain barrierPittsburgh compound BIn vitroChemistryTranslocator proteinRadioligandNuclear medicineNeurosciencePathologyMedicineAlzheimer's diseasePsychologyBiochemistryNeuroinflammationDiseaseCentral nervous systemBiology

Abstract

fetched live from OpenAlex

High Resolution Image Download MS PowerPoint Slide [ 18 F]PI-2620 is a promising radiopharmaceutical for positron emission tomography (PET) imaging of both Alzheimer’s disease (AD) and non-Alzheimer’s disease (non-AD) tauopathies in humans. An array of fluorinated derivatives of the carbazole scaffold of PI-2620 were synthesized and evaluated. In vitro binding assays with [ 3 H]PI-2620 in human tissues with AD, progressive supranuclear palsy, and corticobasal degeneration, combined with in silico predictions of blood–brain barrier permeability, led to the selection and radiosynthesis of [ 18 F]F-4 as a promising radiotracer. In vivo PET imaging with [ 18 F]F-4 in healthy rats showed brain uptake and kinetics suitable for neuroimaging, similar to those of [ 18 F]PI-2620. A first-in-human PET imaging study in a healthy subject as well as a patient with AD, in comparison with [ 18 F]PI-2620 in the same AD subject, confirmed that [ 18 F]F-4 is an alternative radiopharmaceutical for imaging tau protein.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Non-randomized trial · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0020.001

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.300
Teacher spread0.281 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designNon-randomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations3
Published2025
Admission routes2
Has abstractyes

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