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Radiosynthesis and Preclinical Evaluation of <sup>18</sup>F-Fluoroglycosylated Octreotate for Somatostatin Receptor Imaging

2016· article· en· W2528566954 on OpenAlexaff
Simone Maschauer, Marcus Heilmann, Carmen Wängler, Ralf Schirrmacher, Olaf Prante

Bibliographic record

VenueBioconjugate Chemistry · 2016
Typearticle
Languageen
FieldMedicine
TopicNeuroendocrine Tumor Research Advances
Canadian institutionsUniversity of Alberta
FundersDeutsche Forschungsgemeinschaft
KeywordsChemistryRadiosynthesisSomatostatin receptorSomatostatinRadiochemistryNuclear medicineReceptorPositron emission tomographyInternal medicineBiochemistry

Abstract

fetched live from OpenAlex

Short synthetic octapeptide analogs derived from the native somatostatin peptides SST-14 and SST-28, namely, octreotate (TATE) or octreotide (TOC), bind with high affinity to somatostatin receptors (sstr), mainly to subtypes 2 and 5, which are expressed in high density on neuroendocrine tumors (NET). Therefore, radiolabeled TATE or TOC derivatives represent highly valuable imaging probes for NET diagnosis by positron emission tomography (PET). The aim of our study was the development of an 18 F-labeled octreotate analog as an alternative radiotracer for the clinically established 68 Ga-DOTATOC and 68 Ga-DOTATATE. We applied our previously developed method based on copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) to the radiosynthesis of 18 F-fluoroglycosylated TATE ([ 18 F]FGlc-TATE). [ 18 F]FGlc-TATE was obtained in high yields of 19–22% (non-decay-corrected, referred to [ 18 F]fluoride) and in high specific activities of 32–106 GBq/μmol. [ 18 F]FGlc-TATE showed high affinity to sstr expressed on AR42J cells (IC 50 = 4.2 nM) with fast and high internalization, and a beneficial logD 7.4 of −1.8. In AR42J tumor bearing nude mice, [ 18 F]FGlc-TATE showed high and specific tumor uptake of 5.6%ID/g at 60 min post-injection, as determined by blocking experiments using octreotide, and fast clearance from other organs, resulting in excellent tumor-to-blood ratios increasing from 9 to 17 from 30 to 60 min post-injection. Small animal PET studies revealed high uptake of [ 18 F]FGlc-TATE in the tumor which could be blocked with octreotide by >99%. Overall, [ 18 F]FGlc-TATE revealed excellent in vitro and in vivo properties and is therefore a viable alternative 18 F-labeled radiopeptide for imaging somatostatin receptor-positive tumors by PET.

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)0.004
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 score0.055
Threshold uncertainty score0.806

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.004
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)0.0010.000

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 head0.049
GPT teacher head0.360
Teacher spread0.311 · 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

Citations25
Published2016
Admission routes1
Has abstractyes

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