Light-Triggered Radiochemical Synthesis: A Novel ¹⁸F-Labelling Strategy Using Photoinducible Click Reaction to Prepare PET Imaging Probes

Abstract

Novel probe development for positron emission tomography (PET) is leading to expanding the scope of molecular imaging. To begin responding to challenges, several biomaterials such as natural products and small molecules, peptides, engineered proteins including affibodies, and antibodies have been used in the development of targeted molecular imaging probes. To prepare radiotracers, a few bioactive materials are unique challenges to radiolabelling because of their complex structure, poor stability, poor solubility in aqueous or chemical organic solutions, and sensitivity to temperature and nonphysiological pH. To overcome these challenges, we developed a new radiolabelling strategy based on photoactivated 1,3-dipolar cycloaddition between alkene dipolarophile and tetrazole moiety containing compounds. Herein, we describe a light-triggered radiochemical synthesis via photoactivated click reaction to prepare 18F-radiolabelled PET tracers using small molecular and RGD peptide.

Ultrafast Photoclick Reaction for Selective 18F-Positron Emission Tomography Tracer Synthesis in Flow

“…Highly beneficial is that photoclick reactions can combine important requirements to provide a practical indirect labeling protocol, such as high functional group tolerance, ambient reaction conditions, and easy operation in a photoflow reactor, and, importantly, one might achieve extremely high reaction rates without the need for additional reagents or catalysts. The outstanding possibilities offered by photochemical reactions have recently been recognized in several radiochemical applications, i.e., a methylation protocol for 11 C-PET ligand synthesis, photo-redox catalysis for 18 F–C bond formation, photoactivatable aryl azides, and photo-triggered reaction of tetrazoles for radiosynthesis of 89 Zr-labeled proteins. − However, so far a very limited number of photochemical transformations has been utilized as a key step in the indirect labeling of 18 F-PET tracers, − and none of them provides the modularity and selectivity typical of click reactions.…”