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

J Labelled Comp Radiopharm. 2024 May 30;67(6):245-249. doi: 10.1002/jlcr.4079. Epub 2023 Dec 20.

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; [11C]AZD4747; carbonylation; carbon‐11; validation.

Publication types

  • Validation Study

MeSH terms

  • Carbon Radioisotopes* / chemistry
  • Humans
  • Proto-Oncogene Proteins p21(ras)* / antagonists & inhibitors
  • Proto-Oncogene Proteins p21(ras)* / metabolism
  • Radiochemistry
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / pharmacokinetics

Substances

  • Carbon Radioisotopes
  • Proto-Oncogene Proteins p21(ras)
  • Radiopharmaceuticals
  • KRAS protein, human