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Record W3213181298 · doi:10.3389/fnume.2021.772289

Radiosynthesis of [11C]Ibrutinib via Pd-Mediated [11C]CO Carbonylation: Preliminary PET Imaging in Experimental Autoimmune Encephalomyelitis Mice

2021· article· en· W3213181298 on OpenAlexafffund
Anton Lindberg, Amanda J. Boyle, Junchao Tong, Michael B. Harkness, Armando García, Tritin Tran, Dongxu Zhai, Fang Liu, David J. Donnelly, Neil Vasdev

Bibliographic record

VenueFrontiers in Nuclear Medicine · 2021
Typearticle
Languageen
FieldMedicine
TopicChronic Lymphocytic Leukemia Research
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersOntario Ministry of Research and InnovationCanada Research ChairsCanada Excellence Research Chairs, Government of CanadaCanada Foundation for InnovationAzrieli FoundationCentre for Addiction and Mental Health
KeywordsIbrutinibChemistryRadiosynthesisBruton's tyrosine kinasePositron emission tomographyExperimental autoimmune encephalomyelitisNuclear medicineRadiochemistryMedicineInternal medicineTyrosine kinaseImmunologyMultiple sclerosisReceptorBiochemistryLeukemia

Abstract

fetched live from OpenAlex

Ibrutinib is a first-generation Bruton's tyrosine kinase (BTK) inhibitor that has shown efficacy in autoimmune diseases and has consequently been developed as a positron emission tomography (PET) radiotracer. Herein, we report the automated radiosynthesis of [ 11 C]ibrutinib through 11 C-carbonylation of the acrylamide functional group, by reaction of the secondary amine precursor with [ 11 C]CO, iodoethylene, and palladium–NiXantphos. [ 11 C]Ibrutinib was reliably formulated in radiochemical yields of 5.4% ± 2.5% (non-decay corrected; n = 9, relative to starting [ 11 C]CO 2 ), radiochemical purity >99%, and molar activity of 58.8 ± 30.8 GBq/μmol (1.55 ± 0.83 Ci/μmol). Preliminary PET/magnetic resonance imaging with [ 11 C]ibrutinib in experimental autoimmune encephalomyelitis (EAE) mice showed a 49% higher radioactivity accumulation in the spinal cord of mice with EAE scores of 2.5 vs. sham mice.

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 distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.645
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0010.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0020.000

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 head0.009
GPT teacher head0.273
Teacher spread0.264 · 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 teacher head, not a consensus.

Study designBench or experimental
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

Citations10
Published2021
Admission routes2
Has abstractyes

Explore more

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