This title appears in the Scientific Report :
2009
Please use the identifier:
http://dx.doi.org/10.2967/jnumed.109.063297 in citations.
Three-step, 'one-pot' radiosynthesis of 6-fluoro-3,4-dihydroxy-l-phenylalanine by isotopic exchange
Three-step, 'one-pot' radiosynthesis of 6-fluoro-3,4-dihydroxy-l-phenylalanine by isotopic exchange
The (18)F-labeled aromatic amino acid 6-fluoro-3,4-dihydroxy-L-phenylalanine (6-(18)F-fluoro-L-DOPA) is widely used as a radiopharmaceutical in neurologic and oncologic PET. In this study, a novel approach to the preparation of carrier-added (CA) 6-(18)F-fluoro-L-DOPA in 3 radiosynthesis steps was d...
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Personal Name(s): | Wagner, F.M. |
---|---|
Ermert, J. / Coenen, H. H. | |
Contributing Institute: |
Nuklearchemie; INM-5 JARA-BRAIN; JARA-BRAIN |
Published in: | Journal of Nuclear Medicine Journal of nuclear medicine, 50 50 (2009 2009) 10 10, S. 1724-1729 1724-1729 |
Imprint: |
New York, NY
Society of Nuclear Medicine
2009
2009-09-16 2009-10-01 2009-10-01 |
Physical Description: |
1724 - 1729 |
PubMed ID: |
19759110 |
DOI: |
10.2967/jnumed.109.063297 |
Document Type: |
Journal Article |
Research Program: |
Funktion und Dysfunktion des Nervensystems |
Series Title: |
Journal of Nuclear Medicine
50 |
Subject (ZB): | |
Publikationsportal JuSER |
The (18)F-labeled aromatic amino acid 6-fluoro-3,4-dihydroxy-L-phenylalanine (6-(18)F-fluoro-L-DOPA) is widely used as a radiopharmaceutical in neurologic and oncologic PET. In this study, a novel approach to the preparation of carrier-added (CA) 6-(18)F-fluoro-L-DOPA in 3 radiosynthesis steps was developed and evaluated; in this approach, direct nucleophilic (18)F fluorination of a protected amino acid derivative was used. The method currently used for the routine preparation of 6-(18)F-fluoro-L-DOPA by electrophilic labeling is limited to the production of small amounts of activity at high costs. Alternative syntheses based on the advantage of large-scale production of nucleophilic (18)F-fluoride, however, either have resulted in insufficient enantiomeric purity or are difficult to automate because of the complexity of the necessary multiple steps.An isotopic exchange reaction on the precursor (2S,5S)-tert-butyl-5-(4-benzyloxy-2-fluoro-5-formylbenzyl)-2-tert-butyl-3-methyl-4-oxoimidazolidine-1-carboxylate was used. The formyl group served as the activating group in the (18)F-for-(19)F exchange with tetrabutylammonium bicarbonate for anion activation in N,N-dimethylformamide. The intermediate was converted to a hydroxy group by Baeyer-Villiger oxidation with meta-chloroperbenzoic acid. After final deprotection with hydrobromic acid, CA 6-(18)F-fluoro-L-DOPA was isolated by high-performance liquid chromatography.The precursor was obtained by an 11-step organic synthesis. The optimized isotopic (18)F exchange proceeded with a radiochemical yield of about 50%. The complete preparation and isolation of CA 6-(18)F-fluoro-L-DOPA thus far are possible with a radiochemical yield of about 22%, within a synthesis time of 105 min, and at a much higher specific activity than with the electrophilic method. The enantiomeric excess of the desired L-isomer was greater than 96%.The pathway to 6-(18)F-fluoro-L-DOPA by isotopic exchange not only is more efficient but also is suited to automation as a "one-pot" procedure. |