Synthesis of [18F]aryltriflones for PET imaging

• Applicant: Dr. Lukas Veth
• Subject Area: Organic Molecular Chemistry - Synthesis and Characterisation ; Radiology
• Term: from 2023 to 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 519969214

• Final Report Year: 2025

Final Report Abstract

Positron emission tomography (PET) is a nuclear imaging technique used in clinical routine for the diagnosis of a range of diseases, e.g., cancer and neurodegenerative diseases, and for drug development. It uses so-called PET tracers which are compounds that are labeled with dedicated radioactive nuclides, the most important being fluorine-18 (or 18F). Currently, the development of new PET tracers is limited because methods for their preparation are not sufficiently well developed. In this project, new synthetic methods for the radiolabeling with 18F for the preparation of PET tracers were developed. Specifically, strategies for the incorporation of 18F-trifluoromethyl groups (CF3-18F) were evaluated by exploring the reactivity of recently reported labeling reagents, [18F]fluoroform and [18F]Ruppert-Prakash reagent. This enabled the synthesis of several previously inaccessible structural motifs, among them 18F-labeled aryl triflones. In addition, a new labeling reagent, [18F]trifluoroiodomethane, was synthesized and utilized for radiolabeling by photoredox-mediated radical [18F]trifluoromethylation, a previously unexplored reaction pathway. The results of this project can be used in PET tracer development programs in the whole world and will therefore make a contribution to the advancement of modern healthcare.

Publications

• Synthesis of [18F]Aryl trifluoromethyl sulfones, -sulfoxides, and -sulfides. Nuclear Medicine and Biology, 126-127, 108515.
  Veth, Lukas; Windhorst, Albert & Vugts, Danielle
  
• [18F]CF3I – Enabling Photoredox-mediated Radical [18F]Trifluoromethylation for Positron Emission Tomography. American Chemical Society (ACS).
  Veth, Lukas; Windhorst, Albert D. & Vugts, Danielle J.
  
• [18F]Trifluoroiodomethane – Enabling Photoredox‐mediated Radical [18F]Trifluoromethylation for Positron Emission Tomography. Angewandte Chemie, 137(4).
  Veth, Lukas; Windhorst, Albert D. & Vugts, Danielle J.
  
• Synthesis of 18F-labelled aryl trifluoromethyl ketones with improved molar activity. Chemical Communications, 60(53), 6801-6804.
  Veth, Lukas; Windhorst, Albert D. & Vugts, Danielle J.
  
• Synthesis of 18F‐labeled Aryl Trifluoromethyl Sulfones, ‐Sulfoxides, and ‐Sulfides for Positron Emission Tomography. Angewandte Chemie, 136(27).
  Veth, Lukas; Windhorst, Albert D. & Vugts, Danielle J.