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Record W2974156609 · doi:10.1002/jlcr.3805

“In‐loop” carbonylation—A simplified method for carbon‐11 labelling of drugs and radioligands

2019· article· en· W2974156609 on OpenAlex
Mélodie Ferrat, Kenneth Dahl, Christer Halldin, Magnus Schou

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueJournal of Labelled Compounds and Radiopharmaceuticals · 2019
Typearticle
Languageen
FieldMedicine
TopicMedical Imaging Techniques and Applications
Canadian institutionsUniversity of TorontoCentre for Addiction and Mental Health
FundersHorizon 2020 Framework ProgrammeH2020 Marie Skłodowska-Curie ActionsKarolinska InstitutetEuropean Commission
KeywordsRadioligandChemistryCarbonylationYield (engineering)High-performance liquid chromatographyTriethylamineRacloprideBenzoic acidChromatographyCarbon monoxideNuclear chemistryDopamine receptor D2Organic chemistryMaterials scienceReceptorCatalysis

Abstract

fetched live from OpenAlex

Abstract Transition‐metal mediated carbonylation with 11 C‐labelled carbon monoxide ([ 11 C]CO) is a versatile method for introducing 11 C ( t 1/2 = 20.3 min) into drugs and radioligands for subsequent use in positron emission tomography (PET). The aim of the current study was to perform the 11 C‐carbonylation reaction on the interior surface of a stainless‐steel loop used for high performance liquid chromatography (HPLC). In the experimental setup, cyclotron produced 11 C‐labelled carbon dioxide ([ 11 C]CO 2 ) was converted to [ 11 C]CO by reduction over heated Molybdenum and swept into an HPLC loop pre‐charged with the appropriate reaction mixture. Following a 5 min reaction, the radiochemical purity (RCP) and the trapping efficiency (TE) of the reaction mixture was determined. After optimization, [ 11 C] N ‐Benzylbenzamide was obtained in quantitative radiochemical yield (RCY) following a 5 min reaction at room temperature. The methodology was further applied to label [ 11 C]benzoic acid (RCP≥99%, TE>91%), [ 11 C]methyl benzoate (RCP≥99%, TE>93%) and [ 11 C]phthalide (RCP≥99%, TE>88%). A set of pharmaceuticals was finally radiolabelled using non‐optimized conditions. Excellent yields were obtained for the histamine‐3 receptor radioligand [ 11 C]AZ13198083, the oncology drug [ 11 C]olaparib and the dopamine D2 receptor radioligand [ 11 C]raclopride, whereas a moderate yield was observed for the high‐affinity dopamine D2 receptor radioligand [ 11 C]FLB457. The presented “in‐loop” process proved efficient for diverse 11 C‐carbonylations, providing [ 11 C]amides, [ 11 C]esters and [ 11 C]carboxylic acids in moderate to excellent RCYs. Based on the advantages associated with performing the radiolabelling step as an integrated part of the purification system, this methodology may become a valuable addition to the toolbox of methodologies used for 11 C‐carbonylation of drugs and radioligands for 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.

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 categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.693
Threshold uncertainty score0.446

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
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 head0.026
GPT teacher head0.378
Teacher spread0.351 · 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