Lugato B, Stucchi S, Ciceri S, Iannone M N, Turolla E A, Giuliano L, Chinello C, Todde S, Ferraboschi P
Department of Medicine and Surgery, Tecnomed Foundation, University of Milano-Bicocca, Monza, Italy.
Dipartimento di Biotecnologie Mediche e Medicina Traslazionale, Università degli Studi di Milano, Milan, Italy.
J Labelled Comp Radiopharm. 2017 Aug;60(10):466-480. doi: 10.1002/jlcr.3529. Epub 2017 Aug 2.
As an effort to improve F-radiolabeling of biomolecules in method robustness and versatility, we report the synthesis and radiolabeling of a new azido precursor potentially useful for the so-called "click reaction," in particular the ligand-free version of the copper(I)-catalyzed alkyne-azide cycloaddition. The new azido precursor may help to overcome problems sometimes exhibited by most of the currently used analogues, as it is safe to handle and it displays long-term chemical stability, thus facilitating the development of new radiolabeling procedures. Moreover, the formed F-labeled 1,2,3-triazole is potentially metabolically stable and could enhance the in vivo circulation time. The above azido precursor was successfully radiolabeled with F, with 51% radiochemical yield (nondecay-corrected). As a proof of concept, the F-labeled azide was then tested with a suitable alkyne functionalized aminoacid (l-propargylglycine), showing 94% of conversion, and a final radiochemical yield of 27% (>99% radiochemical purity), nondecay-corrected, with a total preparation time of 104 minutes.
为了提高生物分子F放射性标记的方法稳健性和通用性，我们报道了一种新的叠氮基前体的合成及放射性标记，该前体可能对所谓的“点击反应”有用，特别是铜（I）催化的无配体炔烃-叠氮环加成反应。这种新的叠氮基前体可能有助于克服目前大多数类似物有时出现的问题，因为它易于操作且具有长期化学稳定性，从而促进新放射性标记程序的开发。此外，形成的F标记的1,2,3-三唑可能具有代谢稳定性，并可延长体内循环时间。上述叠氮基前体成功地用F进行了放射性标记，放射化学产率为51%（未进行衰变校正）。作为概念验证，然后用合适的炔烃官能化氨基酸（L-炔丙基甘氨酸）测试了F标记的叠氮化物，转化率为94%，最终放射化学产率为27%（放射化学纯度>99%），未进行衰变校正，总制备时间为104分钟。
