Radiosynthesis and bioconjugation of [18F]FPy5yne, a prosthetic group for the 18F labeling of bioactive peptides
Radiosynthesis and bioconjugation of [18F]FPy5yne, a prosthetic group for the 18F labeling of bioactive peptides
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DOI：
10.1002/jlcr.1561
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发表时间：
2008-11-01
影响因子：
1.8
通讯作者：
Adam, Michael J.
中科院分区：
文献类型：
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作者：
Inkster, James A. H.;Guerin, Brigitte;Adam, Michael J.
一种新的基于F-18的假体基团已经被制备出来，用于标记叠氮修饰的多肽用于PET成像。通过对相应的2-硝基(2)或2-三甲基三氟甲磺酸基吡啶(3)进行有效的亲核杂环取代，合成了2-[F-18]-3-(六-5-芳氧基)吡啶([F-18]FPy5 yne，[F-18]-1)。通过放射TLC(15min，110℃，DMSO)，[F-18]FPy5 yne的最佳放化产率为91%。从3开始，放射TLC的最佳放化产率为93%(15min，110℃，MeCN)。在铜稳定配体三(苄基三唑甲基)胺和N，N-二异丙基乙胺存在下，通过铜-L介导的惠斯根[3+2]环加成反应，将纯化的[F-18][F-18]FP y5 yne连接到模型肽N-3-(CH2)(4)-CO-YK-RI-OH。经放射高效液相色谱法测定，生物偶联放化产率平均为89%+/-8.6%(n=4)。从轰击结束收集的未衰变校正的最佳修饰肽的放化产率为5.8%(衰变校正后的产率为18.7%)，从合成开始的总制备时间为160min。
A new F-18-based prosthetic group has been prepared for the labeling of azide-modified peptides for use in PET imaging. 2-[F-18]fluoro-3-(hex-5-ynyloxy)pyridine ([F-18]FPy5yne, [F-18]-1) was prepared via efficient nucleophilic heteroaromatic substitution of either the corresponding 2-nitro (2) or 2-trimethylammonium trifluoromethanesulfonate pyridine (3). Best radiochemical yield of [F-18]FPy5yne from 2 was 91% by radioTLC (15 min, 110 degrees C, DMSO). From 3, best radiochemical yield by radioTLC was 93% (15 min, 110 degrees C, MeCN). HPLC-purified [F-18]FPy5yne was ligated to model pepticle N-3-(CH2)(4)-CO-YK-RI-OH by way of Cu-l-mediated Huisgen [3+2] cycloaddition in the presence of copper-stabilizing ligand tris(benzyl-triazolylmethyl)amine (TBTA) and N,N-diisopropylethylamine (DIEA). Bioconjugate radiochemical yields were obtained in average yields of 89% +/- 8.6% (n = 4), as judged by radioHPLC. Best non-decay-corrected, collected radiochemical yield of modified pepticle from end-of-bombardment was 5.8% (18.7% decay-corrected), with a total preparation time of 160 min from start of synthesis.