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Record W4317915641 · doi:10.21203/rs.3.rs-2500498/v1

Intracellular Acidification in a Rat C6 Glioma Model Following Cariporide Injection Monitored by Chemical Exchange Saturation Transfer Magnetic Resonance Imaging

2023· preprint· en· W4317915641 on OpenAlexafffund
Maryam Mozaffari, Nivin N. Nyström, Alex Li, Miranda Bellyou, Timothy J. Scholl, Robert Bartha

Bibliographic record

VenueResearch Square · 2023
Typepreprint
Languageen
FieldMaterials Science
TopicLanthanide and Transition Metal Complexes
Canadian institutionsOntario Institute for Cancer ResearchWestern University
FundersCanadian Institutes of Health ResearchCanada First Research Excellence Fund
KeywordsGliomaChemistryMagnetic resonance imagingIn vivoIntracellular pHBrain tissueNuclear magnetic resonanceNuclear medicineIntracellularMedicinePathologyCancer researchInternal medicineBiologyBiochemistryRadiology

Abstract

fetched live from OpenAlex

Abstract Gliomas are the most common primary brain tumors. Selective acidification of cancerous tissue induced pharmacologically may slow tumor growth and can be detected using magnetic resonance imaging (MRI). The sodium proton exchanger inhibitor cariporide can selectively acidify U87MG gliomas in mice. This study aimed to determine whether cariporide could selectively acidify C6 glioma tumors in rats with an intact immune system. C6 glioma cells were implanted in the right brain hemisphere of ten male Wistar rats. Chemical exchange saturation transfer (CEST) MRI (9.4T) was acquired on days 7–8 (N= 10) and 14–15 (N= 10) after implantation to measure in vivo tissue intracellular pH (pHi) within the tumors and on the contralateral side. Intracellular pH was basic relative to contralateral tissue at both time points (p < 0.05) assessed using the amine and amide concentration-independent detection (AACID) value. On day 14–15, measurements were made before and up to 160 minutes after cariporide injection (N= 6, dose: 6 mg/kg in 2 mL with 10% DMSO). Twenty minutes after drug injection, the average AACID value in the tumor significantly increased by ∼6.4% compared to pre-injection, corresponding to 0.31 ± 0.20 lower pHi, while in contralateral tissue, AACID value increases significantly by ∼4.3% compared to pre-injection, corresponding to 0.22 ± 0.19 lower pHi. Then the average AACID value returned to the baseline level in both tissues about an hour after the injection before trending back up in contralateral tissue 80 minutes and 100 minutes after injection. Control rats without tumors showed no changes following injection of cariporide in 10% or 1% DMSO. This study demonstrates the sensitivity of CEST-based pH-weighted imaging for monitoring the response of tumors to pharmacologically induced acidification. Although cariporide did induce intracellular acidification in the C6 glioma, this acidification was not tumor selective in this model.

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)0.002
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow)
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 score0.067
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0020.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
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 head0.060
GPT teacher head0.336
Teacher spread0.276 · 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

Citations2
Published2023
Admission routes2
Has abstractyes

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