This title appears in the Scientific Report :
2019
Please use the identifier:
http://dx.doi.org/10.1055/s-0039-1683491 in citations.
Synthesis of N-methyl- and 5-HO-[18F]fluorotryptophans
Synthesis of N-methyl- and 5-HO-[18F]fluorotryptophans
Ziel/Aim:Tryptophan (Trp) metabolism is altered in numerous pathological processes. 7-[F-18]FTrp developed in our group is a promising PET-tracer for imaging of Trp metabolism but is unable to distinguish between the two pathways of Trp metabolization. The aim of this project was the development of...
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Personal Name(s): | Kolks, N. (Corresponding author) |
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Zlatopolskiy, BD / Urusova, EA / Neumaier, B. | |
Contributing Institute: |
Nuklearchemie; INM-5 |
Imprint: |
2019
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DOI: |
10.1055/s-0039-1683491 |
Conference: | 57. Jahrestagung der Deutschen Gesellschaft für Nuklearmedizin, Bremen (Germany), 2019-04-03 - 2019-04-06 |
Document Type: |
Conference Presentation |
Research Program: |
Neuroimaging |
Publikationsportal JuSER |
Ziel/Aim:Tryptophan (Trp) metabolism is altered in numerous pathological processes. 7-[F-18]FTrp developed in our group is a promising PET-tracer for imaging of Trp metabolism but is unable to distinguish between the two pathways of Trp metabolization. The aim of this project was the development of procedures for the preparation of NinMe-6- and 5-HO-7-[F-18]FTrp as PET-probes suitable for selective visualization of the kynurenine or serotonin pathway.Methodik/Methods:Precursor for the radiosynthesis of NinMe-6-[F-18]FTrp, (S,S)-BPB-Ni-NinMe-6-Bpin-Trp, was synthesized starting from 6-bromoindole. Miyaura borylation, followed by a Mannich reaction and quaternization with MeI furnished N,N,N-(6-Bpin-NinMe-indolyl)methyltrimethylammonium iodide. Alkylation of (S)-BPB-Ni-Gly with the latter and Nin-methylation afforded the desired precursor. Boc-7-Bpin-5-AcO-Trp-OtBu was prepared via Ir-catalyzed 2,7-diborylation of Boc-5-AcO-Trp-OtBu, accessible from 5-OH-Trp in three reaction steps, followed by selective 2-deborylation using Bi(OAc)3. Both precursors were radiolabeled according to the protocol of alcohol-enhanced Cu-mediated F-18-fluorination. The decomposition of the labeled precursors under acidic conditions afforded the F-18-labeled amino acids NinMe-6- and 5-HO-7-[F-18]FTrp.Ergebnisse/Results:(S,S)-BPB-Ni-NinMe-6-Bpin-Trp was obtained in a total yield of 13% after 5 steps and Boc-7-BPin-5-AcO-Trp-OtBu in a 12% yield after 5 steps. (S,S)-BPB-Ni-NinMe-6-[F-18]FTrp was produced in RCCs of up to 90%, decomposed to Nin-Me-6-[F-18]FTrp and isolated by HPLC in RCY of 10 – 15%. Boc-5-OAc-7-Bpin-Trp-OtBu was labeled with an RCC of 25% and after deprotection 5-HO-7-[F-18]FTrp was obtained similarly to NinMe-6-[F-18]FTrp but in lower RCY.Schlussfolgerungen/Conclusions:Nin-Me-6- and 5-HO-7-[F-18]FTrp represent promising PET-probes for the delineation of kynurenine and serotonin pathways of Trp metabolism. Both probes were successfully prepared using alcohol-enhanced Cu-mediated radiofluorination. |