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Article

Isotopic Radiolabeling of the Antiretroviral Drug [18F]Dolutegravir for Pharmacokinetic PET Imaging

1
Université Paris-Saclay, Inserm, CNRS, CEA, Laboratoire d’Imagerie Biomédicale Multimodale Paris-Saclay (BioMaps), 91401 Orsay, France
2
GSK Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, UK
3
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
4
ViiV Healthcare, 980 Great West Road, London TW8 9GS, UK
*
Author to whom correspondence should be addressed.
Academic Editor: Klaus Kopka
Pharmaceuticals 2022, 15(5), 587; https://doi.org/10.3390/ph15050587
Received: 11 March 2022 / Revised: 3 May 2022 / Accepted: 5 May 2022 / Published: 10 May 2022
(This article belongs to the Section Radiopharmaceutical Sciences)
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. View Full-Text
Keywords: fluorine-18; radiolabeling; dolutegravir; PET imaging fluorine-18; radiolabeling; dolutegravir; PET imaging
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MDPI and ACS Style

Tisseraud, M.; Goutal, S.; Bonasera, T.; Goislard, M.; Desjardins, D.; Le Grand, R.; Parry, C.M.; Tournier, N.; Kuhnast, B.; Caillé, F. Isotopic Radiolabeling of the Antiretroviral Drug [18F]Dolutegravir for Pharmacokinetic PET Imaging. Pharmaceuticals 2022, 15, 587. https://doi.org/10.3390/ph15050587

AMA Style

Tisseraud M, Goutal S, Bonasera T, Goislard M, Desjardins D, Le Grand R, Parry CM, Tournier N, Kuhnast B, Caillé F. Isotopic Radiolabeling of the Antiretroviral Drug [18F]Dolutegravir for Pharmacokinetic PET Imaging. Pharmaceuticals. 2022; 15(5):587. https://doi.org/10.3390/ph15050587

Chicago/Turabian Style

Tisseraud, Marion, Sébastien Goutal, Thomas Bonasera, Maud Goislard, Delphine Desjardins, Roger Le Grand, Chris M. Parry, Nicolas Tournier, Bertrand Kuhnast, and Fabien Caillé. 2022. "Isotopic Radiolabeling of the Antiretroviral Drug [18F]Dolutegravir for Pharmacokinetic PET Imaging" Pharmaceuticals 15, no. 5: 587. https://doi.org/10.3390/ph15050587

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