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

Qunchao Zhao, Sanjay Telu (), Shuiyu Lu and Victor W. Pike ()
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Qunchao Zhao: National Institutes of Health
Sanjay Telu: National Institutes of Health
Shuiyu Lu: National Institutes of Health
Victor W. Pike: National Institutes of Health

Nature Communications, 2025, vol. 16, issue 1, 1-10

Abstract: 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 (t1/2 = 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.

Date: 2025
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DOI: 10.1038/s41467-025-56897-5

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