Validation of a good manufacturing practice procedure for the production of [11C]AZD4747, a CNS penetrant KRASG12c inhibitor

Miguel A. Cortés González; Antonia A. Högnäsbacka; Christer Halldin; Magnus Schou

doi:https://doi.org/10.1002/jlcr.4079

Validation of a good manufacturing practice procedure for the production of [11C]AZD4747, a CNS penetrant KRASG12c inhibitor

Miguel A. Cortés González, Antonia A. Högnäsbacka, Christer Halldin, Magnus Schou

Radiology and Nuclear Medicine (VUmc)

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

AZD4747 is a KRASG12C inhibitor recently shown to cross the non-human primate blood-brain barrier efficiently. In the current study, a GMP-compliant production of [11C]AZD4747 was developed to enable PET studies in human subjects. The validated procedure afforded [11C]AZD4747 as an injectable solution in good radioactivity yield (1656 ± 532 MBq), excellent radiochemical purity (100%), and a molar activity of 77 ± 13 GBq/μmol at the end of the synthesis, which took 46 ± 1 min from the end of the bombardment. Quality control on the final product was performed satisfactorily and met all acceptance criteria.

Original language	English
Journal	Journal of Labelled Compounds and Radiopharmaceuticals
Early online date	2023
DOIs	https://doi.org/10.1002/jlcr.4079
Publication status	E-pub ahead of print - 2023

Keywords

AZD4747
GMP
KRAS
PET
[ C]AZD4747
carbon-11
carbonylation
validation

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https://doi.org/10.1002/jlcr.4079

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title = "Validation of a good manufacturing practice procedure for the production of [11C]AZD4747, a CNS penetrant KRASG12c inhibitor",

abstract = "AZD4747 is a KRASG12C inhibitor recently shown to cross the non-human primate blood-brain barrier efficiently. In the current study, a GMP-compliant production of [11C]AZD4747 was developed to enable PET studies in human subjects. The validated procedure afforded [11C]AZD4747 as an injectable solution in good radioactivity yield (1656 ± 532 MBq), excellent radiochemical purity (100%), and a molar activity of 77 ± 13 GBq/μmol at the end of the synthesis, which took 46 ± 1 min from the end of the bombardment. Quality control on the final product was performed satisfactorily and met all acceptance criteria.",

keywords = "AZD4747, GMP, KRAS, PET, [ C]AZD4747, carbon-11, carbonylation, validation",

author = "{Cort{\'e}s Gonz{\'a}lez}, {Miguel A.} and H{\"o}gn{\"a}sbacka, {Antonia A.} and Christer Halldin and Magnus Schou",

note = "Funding Information: MACG and AAH contributed equally to this work and are co‐first authors of this publication. We are grateful to all members of the PET group at the Karolinska Institutet. The study was funded by AstraZeneca. MS is grateful for financial support from the Knut and Alice Wallenberg Foundation (Dnr: 2018.0066). Publisher Copyright: {\textcopyright} 2023 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.",

year = "2023",

doi = "https://doi.org/10.1002/jlcr.4079",

language = "English",

journal = "Journal of Labelled Compounds and Radiopharmaceuticals",

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publisher = "John Wiley and Sons Ltd",

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T1 - Validation of a good manufacturing practice procedure for the production of [11C]AZD4747, a CNS penetrant KRASG12c inhibitor

AU - Cortés González, Miguel A.

AU - Högnäsbacka, Antonia A.

AU - Halldin, Christer

AU - Schou, Magnus

N1 - Funding Information: MACG and AAH contributed equally to this work and are co‐first authors of this publication. We are grateful to all members of the PET group at the Karolinska Institutet. The study was funded by AstraZeneca. MS is grateful for financial support from the Knut and Alice Wallenberg Foundation (Dnr: 2018.0066). Publisher Copyright: © 2023 The Authors. Journal of Labelled Compounds and Radiopharmaceuticals published by John Wiley & Sons Ltd.

PY - 2023

Y1 - 2023

N2 - AZD4747 is a KRASG12C inhibitor recently shown to cross the non-human primate blood-brain barrier efficiently. In the current study, a GMP-compliant production of [11C]AZD4747 was developed to enable PET studies in human subjects. The validated procedure afforded [11C]AZD4747 as an injectable solution in good radioactivity yield (1656 ± 532 MBq), excellent radiochemical purity (100%), and a molar activity of 77 ± 13 GBq/μmol at the end of the synthesis, which took 46 ± 1 min from the end of the bombardment. Quality control on the final product was performed satisfactorily and met all acceptance criteria.

AB - AZD4747 is a KRASG12C inhibitor recently shown to cross the non-human primate blood-brain barrier efficiently. In the current study, a GMP-compliant production of [11C]AZD4747 was developed to enable PET studies in human subjects. The validated procedure afforded [11C]AZD4747 as an injectable solution in good radioactivity yield (1656 ± 532 MBq), excellent radiochemical purity (100%), and a molar activity of 77 ± 13 GBq/μmol at the end of the synthesis, which took 46 ± 1 min from the end of the bombardment. Quality control on the final product was performed satisfactorily and met all acceptance criteria.

KW - AZD4747

KW - GMP

KW - KRAS

KW - PET

KW - [ C]AZD4747

KW - carbon-11

KW - carbonylation

KW - validation

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DO - https://doi.org/10.1002/jlcr.4079

M3 - Article

C2 - 38124264

SN - 0362-4803

JO - Journal of Labelled Compounds and Radiopharmaceuticals

JF - Journal of Labelled Compounds and Radiopharmaceuticals

ER -

Validation of a good manufacturing practice procedure for the production of [11C]AZD4747, a CNS penetrant KRASG12c inhibitor

Abstract

Keywords

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