Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanes

Abstract Positron emission tomography (PET) is an advanced biomedical imaging modality that relies on well-designed radiotracers to report on specific protein targets and processes occurring in living animals and humans. Cyclotron-produced short-lived fluorine-18 (t 1/2 = 109.8 min) is widely used t...

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Main Authors: Qunchao Zhao, Sanjay Telu, Shuiyu Lu, Victor W. Pike
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-56897-5
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author Qunchao Zhao
Sanjay Telu
Shuiyu Lu
Victor W. Pike
author_facet Qunchao Zhao
Sanjay Telu
Shuiyu Lu
Victor W. Pike
author_sort Qunchao Zhao
collection DOAJ
description Abstract Positron emission tomography (PET) is an advanced biomedical imaging modality that relies on well-designed radiotracers to report on specific protein targets and processes occurring in living animals and humans. Cyclotron-produced short-lived fluorine-18 (t 1/2 = 109.8 min) is widely used to radiolabel tracers for PET. Herein we aim to expand the chemical space available for PET tracer development to include structures with 18F-labeled α,α-difluoromethylalkyl groups. We report an efficient and broad-scope method for labeling such groups with high molar activities based on a single-step radiofluorination of α-bromo-α-fluoroalkanes. The method is applicable to bioactive compounds and drug-like molecules, and is readily automated for radiotracer production. The unique physical and biochemical features of the α,α-difluoromethyl group can now be exploited in the design of new PET tracers.
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spelling doaj-art-9a860d222626461390c8a068f45e1b772025-08-20T02:12:58ZengNature PortfolioNature Communications2041-17232025-02-0116111010.1038/s41467-025-56897-5Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanesQunchao Zhao0Sanjay Telu1Shuiyu Lu2Victor W. Pike3Molecular Imaging Branch, National Institute of Mental Health, National Institutes of HealthMolecular Imaging Branch, National Institute of Mental Health, National Institutes of HealthMolecular Imaging Branch, National Institute of Mental Health, National Institutes of HealthMolecular Imaging Branch, National Institute of Mental Health, National Institutes of HealthAbstract Positron emission tomography (PET) is an advanced biomedical imaging modality that relies on well-designed radiotracers to report on specific protein targets and processes occurring in living animals and humans. Cyclotron-produced short-lived fluorine-18 (t 1/2 = 109.8 min) is widely used to radiolabel tracers for PET. Herein we aim to expand the chemical space available for PET tracer development to include structures with 18F-labeled α,α-difluoromethylalkyl groups. We report an efficient and broad-scope method for labeling such groups with high molar activities based on a single-step radiofluorination of α-bromo-α-fluoroalkanes. The method is applicable to bioactive compounds and drug-like molecules, and is readily automated for radiotracer production. The unique physical and biochemical features of the α,α-difluoromethyl group can now be exploited in the design of new PET tracers.https://doi.org/10.1038/s41467-025-56897-5
spellingShingle Qunchao Zhao
Sanjay Telu
Shuiyu Lu
Victor W. Pike
Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanes
Nature Communications
title Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanes
title_full Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanes
title_fullStr Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanes
title_full_unstemmed Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanes
title_short Expanding tracer space for positron emission tomography with high molar activity 18F-labeled α,α-difluoromethylalkanes
title_sort expanding tracer space for positron emission tomography with high molar activity 18f labeled α α difluoromethylalkanes
url https://doi.org/10.1038/s41467-025-56897-5
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