Your browser doesn't support javascript.
loading
Isotopic Radiolabeling of the Antiretroviral Drug [18F]Dolutegravir for Pharmacokinetic PET Imaging.
Tisseraud, Marion; Goutal, Sébastien; Bonasera, Thomas; Goislard, Maud; Desjardins, Delphine; Le Grand, Roger; Parry, Chris M; Tournier, Nicolas; Kuhnast, Bertrand; Caillé, Fabien.
Afiliação
  • Tisseraud M; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), 91401 Orsay, France.
  • Goutal S; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), 91401 Orsay, France.
  • Bonasera T; GSK Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK.
  • Goislard M; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), 91401 Orsay, France.
  • Desjardins D; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Viral Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses, 92032 Paris, France.
  • Le Grand R; Université Paris-Saclay, Inserm, CEA, Center for Immunology of Viral, Auto-Immune, Hematological and Viral Diseases (IMVA-HB/IDMIT), Fontenay-aux-Roses, 92032 Paris, France.
  • Parry CM; ViiV Healthcare, 980 Great West Road, London TW8 9GS, UK.
  • Tournier N; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), 91401 Orsay, France.
  • Kuhnast B; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), 91401 Orsay, France.
  • Caillé F; Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d'Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), 91401 Orsay, France.
Pharmaceuticals (Basel) ; 15(5)2022 May 10.
Article em En | MEDLINE | ID: mdl-35631413
Deciphering the drug/virus/host interactions at infected cell reservoirs is a key leading to HIV-1 remission for which positron emission tomography (PET) imaging using radiolabeled antiretroviral (ARV) drugs is a powerful asset. Dolutegravir (DTG) is one of the preferred therapeutic options to treat HIV and can be isotopically labeled with fluorine-18. [18F]DTG was synthesized via a three-step approach of radiofluorination/nitrile reduction/peptide coupling with optimization for each step. Radiofluorination was performed on 2-fluoro-4-nitrobenzonitrile in 90% conversion followed by nitrile reduction using sodium borohydride and aqueous nickel(II) chloride with 72% conversion. Final peptide coupling reaction followed by HPLC purification and formulation afforded ready-to-inject [18F]DTG in 5.1 ± 0.8% (n = 10) decay-corrected radiochemical yield within 95 min. The whole process was automatized using a TRACERlab® FX NPro module, and quality control performed by analytical HPLC showed that [18F]DTG was suitable for in vivo injection with >99% chemical and radiochemical purity and a molar activity of 83 ± 18 GBq/µmol (n = 10). Whole-body distribution of [18F]DTG was performed by PET imaging on a healthy macaque and highlighted the elimination routes of the tracer. This study demonstrated the feasibility of in vivo [18F]DTG PET imaging and paved the way to explore drug/virus/tissues interactions in animals and humans.
Palavras-chave

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Idioma: En Ano de publicação: 2022 Tipo de documento: Article