Production of 6-l-[18F]Fluoro-m-tyrosine in an Automated Synthesis Module for 11C-Labeling.

Viktoriya V Orlovskaya,Raisa N Krasikova,Bernd Neumaier,Olga S Fedorova,Olga F Kuznetsova,Austin S Craig,Boris D Zlatopolskiy

doi:10.3390/molecules26185550

Abstract

6-l-[18F]Fluoro-m-tyrosine (6-l-[18F]FMT) represents a valuable alternative to 6-l-[18F]FDOPA which is conventionally used for the diagnosis and staging of Parkinson’s disease. However, clinical applications of 6-l-[18F]FMT have been limited by the paucity of practical production methods for its automated production. Herein we describe the practical preparation of 6-l-[18F]FMT using alcohol-enhanced Cu-mediated radiofluorination of Bpin-substituted chiral Ni(II) complex in the presence of non-basic Bu4ONTf using a volatile iPrOH/MeCN mixture as reaction solvent. A simple and fast radiolabeling procedure afforded the tracer in 20.0 ± 3.0% activity yield within 70 min. The developed method was directly implemented onto a modified TracerLab FX C Pro platform originally designed for 11C-labeling. This method enables an uncomplicated switch between 11C- and 18F-labeling. The simplicity of the developed procedure enables its easy adaptation to other commercially available remote-controlled synthesis units and paves the way for a widespread application of 6-l-[18F]FMT in the clinic.

Highlights

Assessing the metabolic activity of L-aromatic amino acid decarboxylase (AADC) [1] with 6-L-[18F]fluoro-3,4-dihydroxyphenylalanine (6-L-[18F]FDOPA) PET is widely used for the diagnosis and staging of Parkinson’s disease (PD)
In patients with PD, the activity of AADC in the striatum is reduced to 5–20% of normal levels before cardinal motor symptoms become apparent [2]
Kinetic modeling and quantification of 6-L-[18F]FDOPA uptake is complicated by its peripheral metabolism mediated by catechol O-methyltransferase (COMT)

Summary

Introduction

Assessing the metabolic activity of L-aromatic amino acid decarboxylase (AADC) [1] with 6-L-[18F]fluoro-3,4-dihydroxyphenylalanine (6-L-[18F]FDOPA) PET is widely used for the diagnosis and staging of Parkinson’s disease (PD). The most recent approaches for 18F-labeling of non-activated aromatics rely upon “late-stage radiofluorinations” using a two-step sequence of reactions: radiofluorination of appropriate precursors (iodonium salts, iodonium ylides, nickel complexes, organoborons or stannanes) followed by acid hydrolysis [23].

Results

Conclusion