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Record W3195577248 · doi:10.1002/cmdc.202100279

FOXM1 Inhibitors as Potential Diagnostic Agents: First Generation of a PET Probe Targeting FOXM1 To Detect Triple‐Negative Breast Cancer <i>in vitro</i> and <i>in vivo</i>

2021· article· en· W3195577248 on OpenAlexaff
David Pérez, Seyed Amirhossein Tabatabaei Dakhili, Cody Bergman, Jennifer Dufour, Melinda Wuest, Freimut D. Juengling, Frank Wuest, Carlos A. Velázquez‐Martínez

Bibliographic record

VenueChemMedChem · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicFOXO transcription factor regulation
Canadian institutionsUniversity of Alberta
FundersConsejo Nacional de Ciencia y Tecnología, Paraguay
KeywordsFOXM1Triple-negative breast cancerIn vivoCancer researchIn vitroBreast cancerMedicineCancerChemistryPharmacologyBiologyInternal medicineBiochemistryGenetics

Abstract

fetched live from OpenAlex

Abstract The FOXM1 protein controls the expression of essential genes related to cancer cell cycle progression, metastasis, and chemoresistance. We hypothesize that FOXM1 inhibitors could represent a novel approach to develop 18 F‐based radiotracers for Positron Emission Tomography (PET). Therefore, in this report we describe the first attempt to use 18 F‐labeled FOXM1 inhibitors to detect triple‐negative breast cancer (TNBC). Briefly, we replaced the original amide group in the parent drug FDI‐6 for a ketone group in the novel AF‐FDI molecule, to carry out an aromatic nucleophilic ( 18 F)‐fluorination. AF‐FDI dissociated the FOXM1‐DNA complex, decreased FOXM1 levels, and inhibited cell proliferation in a TNBC cell line (MDA‐MB‐231). [ 18 F]AF‐FDI was internalized in MDA‐MB‐231 cells. Cell uptake inhibition experiments showed that AF‐FDI and FDI‐6 significantly decreased the maximum uptake of [ 18 F]AF‐FDI, suggesting specificity towards FOXM1. [ 18 F]AF‐FDI reached a tumor uptake of SUV=0.31 in MDA‐MB‐231 tumor‐bearing mice and was metabolically stable 60 min post‐injection. These results provide preliminary evidence supporting the potential role of FOXM1 to develop PET radiotracers.

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)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.912

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
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)0.0000.000

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 head0.233
Teacher spread0.224 · 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.

The models applied no category: nothing in the taxonomy fit this work.
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

Citations3
Published2021
Admission routes1
Has abstractyes

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