New F-18 Prosthetic Group via Oxime Coupling
New F-18 Prosthetic Group via Oxime Coupling
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DOI：
10.1021/bc1004262
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发表时间：
2011-04-01
影响因子：
4.7
通讯作者：
Kung, Hank F.
中科院分区：
文献类型：
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作者：
Carberry, Patrick;Lieberman, Brian P.;Kung, Hank F.
合成了一种新的氟-18辅配体5-（1，3-二氧戊环-2-基）-2-（2-（2-（2-氟乙氧基）乙氧基）吡啶[F-18]2。辅配体在短反应时间（10 min）内以高放射化学产率（rcy = 71 +/-2%，n = 3）和优异的放射化学纯度（rcp = 99 +/-1%，n = 3）形成。[F-18]2是一种小的、中性的有机配合物，易于从容易获得的起始材料通过四个步骤合成。它可以在酸性条件下通过肟键锚定到含有氨氧基官能团的靶分子上。我们在此报告了两个实例[F-18]23和[F-18]24，它们是β-淀粉样斑块的潜在成像剂，用该辅基标记。这种方法可用于标记含有氨氧基的蛋白质和肽。将肟标记的复合物[F-18]23和[F-18]24在雄性ICR小鼠中的生物分布与已知的β-淀粉样蛋白斑块指示剂[F-18]-AV-45，florbetapir 1的生物分布进行比较。肟[F-18]23和[F-18]24的尺寸较大，因此应减少血脑屏障（BBB）渗透。肟[F-18]23的脑摄取似乎减少，但仍保留了一些穿过BBB的能力。肟[F-18]24在注射后2 min显示出有希望的结果（0.48%剂量/g），然而，注射后30 min摄取增加（0.92%，剂量/g），表明化合物[F-18]24在体内分解/代谢。我们已经证明了一个通用的协议的氟化物18标记与一个新的辅配体[F-18]2，是容忍对几个官能团，并通过化学选择性肟偶联形成。
A novel fluorine-18 prosthetic ligand, 5-(1,3-dioxolan-2-yl)-2-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)pyridine [F-18]2, has been synthesized. The prosthetic ligand is formed in high radiochemical yield (rcy = 71 +/- 2%, n = 3) with excellent radiochemical purity (rcp = 99 +/- 1%, n = 3) in a short reaction time (10 min). [F-18]2 is a small, neutral, organic complex, easily synthesized in four steps from a readily available starting material. It can be anchored onto a target molecule containing an aminooxy functional group under acidic conditions by way of an oxime bond. We report herein two examples [F-18]23 and [F-18]24, potential imaging agents for beta-amyloid plaques, which were labeled with this prosthetic group. This approach could be used for labeling proteins and peptides containing an aminooxy group. Biodistribution in male ICR mice for both oxime labeled complexes [F-18]23 and [F-18]24 were compared to that of the known beta-amyloid plaque indicator, [F-18]-AV-45, florbetapir 1. Oximes [F-18]23 and [F-18]24 are larger in size and therefore should reduce the blood brain barrier (BBB) penetration. The brain uptake for oxime [F-18]23 appeared to be reduced, but still retained some capability to cross the BBB. Oxime [F-18]24 showed promising results after 2 min post injection (0.48% dose/gram), however, the uptake increased after 30 min post injection (0.92%, dose/gram) suggesting an in vivo decomposition/metabolism of compound [F-18]24. We have demonstrated a general protocol for the fluoride 18 labeling with a new prosthetic ligand [F-18]2 that is tolerant toward several functional groups and is formed via chemoselective oxime coupling.