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Record W3012417687 · doi:10.1186/s13550-020-0611-9

Pharmacokinetics, radiation dosimetry, acute toxicity and automated synthesis of [18F]AmBF3-TATE

2020· article· en· W3012417687 on OpenAlexafffund
Joseph Lau, Jinhe Pan, Étienne Rousseau, Carlos Uribe, Sudhakara Reddy Seelam, Brent W. Sutherland, David M. Perrin, Kuo‐Shyan Lin, François Bénard

Bibliographic record

VenueEJNMMI Research · 2020
Typearticle
Languageen
FieldMedicine
TopicNeuroendocrine Tumor Research Advances
Canadian institutionsSpinal Cord Injury BCUniversity of British ColumbiaBC Cancer Agency
FundersCanadian Institutes of Health ResearchLeading Edge Endowment Fund
KeywordsMedicineDosimetryPharmacokineticsToxicityMedical physicsCardiac imagingNuclear medicineAcute toxicityPharmacologyRadiologyInternal medicine

Abstract

fetched live from OpenAlex

Abstract Introduction [ 18 F]AmBF 3 -TATE is a somatostatin agonist that selectively binds to somatostatin receptor subtype 2 (SSTR2). For clinical translation, pharmacokinetics, radiation dosimetry, and acute toxicity of [ 18 F]AmBF 3 -TATE were assessed with good laboratory practice (GLP) standards. Methods ICR mice were intravenously administered 0.8–2.0 MBq of [ 18 F]AmBF 3 -TATE, with one group pre-injected with 100 μg of [ 19 F]AmBF 3 -TATE 30 min before radiopharmaceutical administration to assess uptake specificity. The mice were euthanized at 0.5, 1, 2, or 4 h post-injection (p.i.). Blood and tissues were collected, weighed, and counted on a gamma counter to determine percentage injected dose per gram (%ID/g). Dosimetry was calculated based on biodistribution data using the mouse and human phantoms included in OLINDA. Acute toxicity was assessed in Sprague-Dawley rats at the dose of 0.742 mg/kg [ 19 F]AmBF 3 -TATE, with a 14-day observation/recovery period. Blood chemistry parameters, gross, and histopathology were evaluated. Body weight change and food consumption were monitored. The production of [ 18 F]AmBF 3 -TATE was automated on a Trasis AllinOne synthesis module. Results [ 18 F]AmBF 3 -TATE was cleared through the renal and hepatobiliary pathway. At 1 h p.i., the pancreas (F, 15.7 ± 3.72 and M 14.3 ± 1.61 %ID/g), stomach (F, 15.3 ± 3.63 and M, 19.0 ± 3.49 %ID/g), and lungs (F, 9.26 ± 2.24 and M, 6.17 ± 6.04 %ID/g) were the organs with the highest specific uptake. Pre-injection with [ 19 F]AmBF 3 -TATE significantly reduced pancreatic uptake (F, 0.13 ± 0.03 and M, 0.18 ± 0.09 %ID/g) at 1 h p.i. For dosimetry extrapolated to the average adult human, the bladder (0.027–0.030 mGy/MBq), pancreas (0.018–0.028 mGy/MBq), and lungs (0.006–0.013 mGy/MBq) are expected to receive the highest doses. No test-item related effects were observed upon evaluation of clinical observations, body weights, food consumption, clinical pathology, gross pathology, and histopathology for acute toxicity. [ 18 F]AmBF 3 -TATE was produced at activity yields of 15.6 ± 4.59 GBq, average molar activity of 435 ± 162 GBq/μmol, and radiochemical purity of 98.0 ± 1.73% with the automated synthesizer. Conclusion [ 18 F]AmBF 3 -TATE binds specifically to SSTR2. At 1000× clinical dose, [ 19 F]AmBF 3 -TATE was well tolerated with no treatment-related adverse effects.

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)0.003
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 score0.064
Threshold uncertainty score0.579

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.003
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
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 head0.068
GPT teacher head0.434
Teacher spread0.367 · 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".

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Citations16
Published2020
Admission routes2
Has abstractyes

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