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<i>p</i>-NO<sub>2</sub>–Bn–H<sub>4</sub>neunpa and H<sub>4</sub>neunpa–Trastuzumab: Bifunctional Chelator for Radiometalpharmaceuticals and <sup>111</sup>In Immuno-Single Photon Emission Computed Tomography Imaging

2017· article· en· W2731595036 on OpenAlexafffund
Sarah Spreckelmeyer, Caterina F. Ramogida, Julie Rousseau, Karen Arane, Ivica Bratanovic, Nadine Colpo, Una Jermilova, Gemma Dias, Iulia Dude, Marı́a de Guadalupe Jaraquemada-Peláez, François Bénard, Paul Schaffer, Chris Orvig

Bibliographic record

VenueBioconjugate Chemistry · 2017
Typearticle
Languageen
FieldMedicine
TopicRadiopharmaceutical Chemistry and Applications
Canadian institutionsBC Cancer AgencyTRIUMFUniversity of British Columbia
FundersNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health Research
KeywordsChemistryBifunctionalChelationTrastuzumabInorganic chemistryCancer

Abstract

fetched live from OpenAlex

Potentially nonadentate (N 5 O 4 ) bifunctional chelator p -SCN–Bn–H 4 neunpa and its immunoconjugate H 4 neunpa–trastuzumab for 111 In radiolabeling are synthesized. The ability of p -SCN–Bn–H 4 neunpa and H 4 neunpa–trastuzumab to quantitatively radiolabel 111 InCl 3 at an ambient temperature within 15 or 30 min, respectively, is presented. Thermodynamic stability determination with In 3+, Bi 3+, and La 3+ resulted in high conditional stability constant ( p M) values. In vitro human serum stability assays have demonstrated both 111 In complexes to have high stability over 5 days. Mouse biodistribution of [ 111 In][In( p -NO 2 –Bn–neunpa)] −, compared to that of [ 111 In][In( p -NH 2 –Bn–CHX-A″–diethylenetriamine pentaacetic acid (DTPA))] 2–, at 1, 4, and 24 h shows fast clearance of both complexes from the mice within 24 h. In a second mouse biodistribution study, the immunoconjugates 111 In-neunpa–trastuzumab and 111 In–CHX-A″–DTPA–trastuzumab demonstrate a similar distribution profile but with slightly lower tumor uptake of 111 In-neunpa–trastuzumab compared to that of 111 In–CHX-A″–DTPA–trastuzumab. These results were also confirmed by immuno-single photon emission computed tomography (immuno-SPECT) imaging in vivo. These initial investigations reveal the acyclic bifunctional chelator p -SCN–Bn–H 4 neunpa to be a promising chelator for 111 In (and other radiometals) with high in vitro stability and also show H 4 neunpa–trastuzumab to be an excellent 111 In chelator with promising biodistribution in 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)0.000
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 score0.010
Threshold uncertainty score0.999

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0010.001
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0010.001
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 head0.021
GPT teacher head0.281
Teacher spread0.260 · 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

Citations42
Published2017
Admission routes2
Has abstractyes

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