Nucleophilic Synthesis of 6-l-[18F]FDOPA. Is Copper-Mediated Radiofluorination the Answer?

Abstract

Positron emission tomography employing 6-l-[18F]fluoro-3,4-dihydroxyphenylalanine (6-l-[18F]FDOPA) is currently a highly relevant clinical tool for detection of gliomas, neuroendocrine tumors and evaluation of Parkinson’s disease progression. Yet, the deficiencies of electrophilic synthesis of 6-l-[18F]FDOPA hold back its wider use. To fulfill growing clinical demands for this radiotracer, novel synthetic strategies via direct nucleophilic 18F-radiloabeling starting from multi-Curie amounts of [18F]fluoride, have been recently introduced. In particular, Cu-mediated radiofluorination of arylpinacol boronates and arylstannanes show significant promise for introduction into clinical practice. In this short review these current developments will be discussed with a focus on their applicability to automation.

Highlight selection of radiochemistry and radiopharmacy developments by editorial board

“…Is Copper-Mediated Radiofluorination the Answer?” published by Raisa N. Krasikova is one of the master examples of what we intend to do in radiochemistry and radiopharmacy: facilitating our lifes in the clinical radiochemistry environment. She chose a molecule of utmost clinical relevance for the diagnosis of different diseases, such as neurological disorders and cancer (Krasikova, 2020 ). However, until now the radiofluorination methods yielding [ 18 F]FDOPA in satisfying activity amounts by fully automated radiosynthesis are still not optimal.…”

Recent Development of Radiofluorination of Boron Agents for Boron Neutron Capture Therapy of Tumor: Creation of 18F-Labeled C-F and B-F Linkages

“…The two principal radiofluorination sources include nucleophilic fluoride [ 18 F - ] and radiofluorine gas [ 18 F]F 2 [ 15 , 16 , 17 , 18 ]. In view of its short half-life (t 1/2 =110 min), the radiofluorination is better arranged at the last step in the whole synthesis.…”

Nucleophilic Radiofluorination Using Tri-tert-Butanol Ammonium as a Bifunctional Organocatalyst: Mechanism and Energetics

“…The 18 F-fluorination [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ] of organic compounds is gaining considerable importance for synthesizing chemicals that can be employed as radiotracers for the diagnosis of various diseases [ 21 , 22 , 23 ] by the highly sensitive imaging technique of positron emission tomography (PET) [ 24 , 25 ]. Electrophilic substitution reactions [ 26 , 27 , 28 ] using the carrier added [ 18 F]F 2 gas were the earlier method for this purpose, but this approach usually suffers from poor radiochemical yields (RCYs) and from the difficulty of handling the [ 18 F]F 2 gas.…”