Li Manshu, Staton Carla, Ma Xinrui, Zhao Weiling, Pan Liqin, Giglio Ben, Berton Haiden S, Wu Zhanhong, Nicewicz David A, Li Zibo
Department of Radiology, Biomedical Research Imaging Center and Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 United States.
Department of Chemistry University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 United States.
ACS Cent Sci. 2024 Jul 18;10(8):1609-1618. doi: 10.1021/acscentsci.4c00407. eCollection 2024 Aug 28.
To avoid the harsh conditions that are oftentimes adopted in direct radiofluorination reactions, conjugation of bioactive ligands with F-labeled prosthetic groups has become an important strategy to construct novel PET agents under mild conditions when the ligands are structurally sensitive. Prosthetic groups with [F]fluoroarene motifs are especially appealing because of their stability in physiological environments. However, their preparation can be intricate, often requiring multistep radiosynthesis with functional group conversions to prevent the decomposition of unprotected reactive prosthetic groups during the harsh radiofluorination. Here, we report a general and simple method to generate a variety of highly reactive F-labeled electrophiles via one-step organophotoredox-mediated radiofluorination. The method benefits from high step-economy, reaction efficiency, functional group tolerance, and easily accessible precursors. The obtained prosthetic groups have been successfully applied in PET agent construction and subsequent imaging studies, thereby demonstrating the feasibility of this synthetic method in promoting imaging and biomedical research.
为避免直接放射性氟化反应中常常采用的苛刻条件，当生物活性配体结构敏感时，将生物活性配体与F标记的辅基共轭已成为在温和条件下构建新型正电子发射断层显像（PET）剂的重要策略。具有[F]氟芳烃基序的辅基因其在生理环境中的稳定性而特别有吸引力。然而，它们的制备可能很复杂，通常需要多步放射性合成以及官能团转化，以防止在苛刻的放射性氟化过程中未受保护的活性辅基分解。在此，我们报告一种通用且简单的方法，通过一步有机光氧化还原介导的放射性氟化生成多种高活性F标记的亲电试剂。该方法具有高步骤经济性、反应效率、官能团耐受性以及易于获得的前体等优点。所获得的辅基已成功应用于PET剂的构建及后续成像研究，从而证明了这种合成方法在促进成像和生物医学研究方面的可行性。
