Ultra-mild 18F-labeling of Biomolecules for PET imaging

We developed a new 18F-radiolabeling methodology for easy preparation of in vivo PET imaging probes, enabling further widespread application of 18F.
Ultra-mild 18F-labeling of Biomolecules for PET imaging

Positron emission tomography (PET) is a powerful molecular imaging technique to visualize and study human physiology by detection of functional positron-emitting radiopharmaceuticals. 18F has obvious advantages as the most widely used radionuclide in PET imaging. 18F-labeled protein probes become more and more frequently used for both diagnosis and therapy monitoring.

But previous harsh labeling conditions such as high temperature and organic solvents are not ideal for direct 18F incorporation to sensitive probe molecules. Thus the preparation of most 18F-labeled proteins uses 18F-labeled intermediates, which could be further coupled to specific functional groups. Multi-step synthesis hampered its widespread applications especially for non-professionals. Several direct aqueous 18F-labeling approaches have been reported using pre-conjugated prosthetic groups as electrophilic Lewis acid fluoride acceptor can afford one-step labeling. Yet, these methods are still not mild or universal enough to realize “shake-and-use” operation.

This study grasps two basic theoretical principles to perform 18F-labeling in water under mild conditions: 1) the highly selective F-acceptors to avoid the OH-interruption; 2) the relative low F substitution energy to fulfill non-energy consuming labeling. This is a universal criterion for further prothesis screen for water-tolerant and spontaneous labeling. We also provided a computational calculation methodology to assess potential candidates, by which some organophosphines were selected as eligible prothesis candidates. So 18F/19F exchange strategy was also adopted to simplify the labeling operation and skip time-consuming HPLC purification. Furthermore, a new chapter of radiolabeling of organofluorophosphine as radiotracers has also been started.

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