Nuklearmedizin 2019; 58(02): 138
DOI: 10.1055/s-0039-1683568
Vorträge
Radiochemie und -pharmazie
Georg Thieme Verlag KG Stuttgart · New York

The Efficient Preparation of Radiolabeled Aromatic Amino Acids via Cu-Mediated Radiofluorination using Ni-complexes

A Craig
1   Jülich Forschungszentrum, INM-5, Cologne
,
N Kolks
1   Jülich Forschungszentrum, INM-5, Cologne
,
E Urusova
1   Jülich Forschungszentrum, INM-5, Cologne
,
BD Zlatopolskiy
1   Jülich Forschungszentrum, INM-5, Cologne
,
B Neumaier
1   Jülich Forschungszentrum, INM-5, Cologne
› Institutsangaben
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Publikationsverlauf

Publikationsdatum:
27. März 2019 (online)

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    Ziel/Aim:

    The aim of this work was to develop a procedure for the preparation of F-18-labeled aromatic amino acids (AAA) via alcohol-enhanced Cu-mediated radiofluorination using Ni-BPX auxiliaries as easily-removable dual-protecting groups.

    Methodik/Methods:

    The Bpin-substituted precursors of radiofluorinated AAA and α-Me-AAA were prepared by alkylation of (S)-Ni-BPB-Gly and (S)-Ni-BPA-(RS)-Ala with the corresponding Bpin-substituted benzyl bromides. Radiolabeling was carried out according to the protocol for alcohol-enhanced1 Cu-mediated radiofluorination as follows: F-18-F- was loaded onto a QMA-cartridge which was subsequently washed with MeOH; F-18-F- was eluted with Et4NHCO3 to a solution of Cu(py)4(OTf)2 and precursor in DMF/nBuOH (2:1), and the reaction mixture was stirred under air at 110 °C for 10 min. Evaporation of the DMA/nBuOH was followed by deprotection using 12 M HCl at 110 °C for 15 min. The acidic solution was evaporated and the tracer was isolated by HPLC.

    Ergebnisse/Results:

    Ni complexes containing 2 – 4-F-18-FPhe, 2 – 4-aMe-F-18-FPhe, 6-F-18-FMT, aMe-6-F-18-FMT, 4-F-18-FTrp and 2-Me-F-18-FTyr residues were obtained in RCCs of 50 – 95%. The purified tracers were isolated in n.d.c 15 – 25% RCYs in excellent radiochemical and enantiomeric purity. Radiosyntheses of 4-F-18-FPhe and 4-F-18-FTrp were implemented to an automated module furnishing tracers in n.d.c RCYs of 25% and 17%, respectively, within 75 – 80 min.

    Schlussfolgerungen/Conclusions:

    Alcohol-enhanced Cu-mediated radiofluorination of BPin substituted Ni-BPX-AAA complexes is a simple, yet powerful method for the fast production of structurally diverse radiolabeled AAAs and alpha-methyl substituted AAAs. The attractiveness of the procedure is highlighted by the accessibility of radiolabeling precursors, high RCYs and easy implementation to an automated module.

    Literatur/References:

    [1] Zichler, J., Niklas, K., Modemann, D., Neumaier, B., Zlatopolskiy, B.; Chemistry – A European Journal, 2017, 23, 3251 – 3256


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