Department of Biomedical Imaging, Genentech Research and Early Development, Genentech Inc., South San Francisco, California, USA.
Nat Protoc. 2011 Oct 13;6(11):1718-25. doi: 10.1038/nprot.2011.390.
An optimized procedure for preparing fluorine-18 ((18)F)-labeled peptides by the copper-catalyzed azide-alkyne 1,3-dipolar cyloaddition (CuAAC) is presented here. The two-step radiosynthesis begins with the microwave-assisted nucleophilic (18)F-fluorination of a precursor containing a terminal p-toluenesulfonyl, terminal azide and polyethylene glycol backbone. The resulting (18)F-fluorinated azide-containing building block is coupled to an alkyne-decorated peptide by the CuAAC. The reaction is accelerated by the copper(I)-stabilizing ligand bathophenanthroline disulfonate and can be performed in either reducing or nonreducing conditions (e.g., to preserve disulfide bonds). After an HPLC purification, (18)F-labeled peptide can be obtained with a 31 ± 6% radiochemical yield (n = 4, decay-corrected from (18)F-fluoride elution) and a specific activity of 39.0 ± 12.4 Ci μmol(-1) within 77 ± 4 min.
这里提出了一种通过铜催化的叠氮-炔基 1,3-偶极环加成（CuAAC）来制备氟-18（(18)F）标记的肽的优化程序。两步放射性合成始于含有末端对甲苯磺酰基、末端叠氮化物和聚乙二醇主链的前体的微波辅助亲核（18）F-氟化。得到的含（18）F-氟化物的叠氮化物砌块通过 CuAAC 与炔基修饰的肽偶联。该反应由铜（I）稳定配体联苯并菲二磺酸盐加速，可以在还原或非还原条件下进行（例如，以保留二硫键）。经过 HPLC 纯化，（18）F 标记的肽可以以 31 ± 6%的放射化学产率（n = 4，从（18）F-氟化物洗脱校正）和 39.0 ± 12.4 Ci μmol(-1)的比活度在 77 ± 4 min 内获得。
