Department of Nuclear Medicine, Cyclotron Research Center, Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-712, Korea.
Bioconjug Chem. 2012 Aug 15;23(8):1680-6. doi: 10.1021/bc3002425. Epub 2012 Jul 23.
We introduce the high-throughput synthesis of various (18)F-labeled peptide tracers by a straightforward (18)F-labeling protocol based on a chemo-orthogonal strain-promoted alkyne azide cycloaddition (SPAAC) using aza-dibenzocyclootyne-substituted peptides as precursors with (18)F-azide synthon to develop peptide based positron emission tomography (PET) molecular imaging probes. The SPAAC reaction and subsequent chemo-orthogonal purification reaction with azide resin proceeded quickly and selectively under physiologically friendly reaction conditions (i.e., toxic chemical reagents-free, aqueous medium, room temperature, and pH ≈7), and provided four (18)F-labeled tumor targetable bioactive peptides such as cyclic Arg-Gly-Asp (cRGD) peptide, bombesin (BBN), c-Met binding peptide (cMBP), and apoptosis targeting peptide (ApoPep) in high radiochemical yields as direct injectable solutions without any HPLC purification and/or formulation processes. In vitro binding assay and in vivo PET molecular imaging study using the (18)F-labeled cRGD peptide also demonstrated a successful application of our (18)F-labeling protocol.
我们介绍了一种高通量合成各种（18）F 标记肽示踪剂的方法，该方法基于基于化学正交应变促进的叠氮化物-炔烃环加成（SPAAC）的简单（18）F 标记方案，使用取代的叠氮化物-二苯并环辛炔的肽作为前体，与（18）F-叠氮化物合成子一起开发基于肽的正电子发射断层扫描（PET）分子成像探针。SPAAC 反应和随后的与叠氮树脂的化学正交纯化反应在生理友好的反应条件下（即无毒化学试剂、水介质、室温、pH ≈7）快速且选择性地进行，并提供了四种（18）F 标记的肿瘤靶向生物活性肽，如环状精氨酸-甘氨酸-天冬氨酸（cRGD）肽、蛙皮素（BBN）、c-Met 结合肽（cMBP）和凋亡靶向肽（ApoPep），作为直接可注射溶液，无需任何 HPLC 纯化和/或制剂过程即可获得高放射化学产率。使用（18）F 标记的 cRGD 肽进行的体外结合测定和体内 PET 分子成像研究也证明了我们（18）F 标记方案的成功应用。
