Isotopic Radiolabeling of the Antiretroviral Drug [<sup>18</sup>F]Dolutegravir for Pharmacokinetic PET Imaging
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...
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Main Authors: | , , , , , , , , , |
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Format: | Book |
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MDPI AG,
2022-05-01T00:00:00Z.
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Summary: | 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. [<sup>18</sup>F]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 [<sup>18</sup>F]DTG in 5.1 ± 0.8% (<i>n</i> = 10) decay-corrected radiochemical yield within 95 min. The whole process was automatized using a TRACERlab<sup>®</sup> FX NPro module, and quality control performed by analytical HPLC showed that [<sup>18</sup>F]DTG was suitable for in vivo injection with >99% chemical and radiochemical purity and a molar activity of 83 ± 18 GBq/µmol (<i>n</i> = 10). Whole-body distribution of [<sup>18</sup>F]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 [<sup>18</sup>F]DTG PET imaging and paved the way to explore drug/virus/tissues interactions in animals and humans. |
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Item Description: | 10.3390/ph15050587 1424-8247 |