A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2
A Modular Platform for the Rapid Site-Specific Radiolabeling of Proteins with 18F Exemplified by Quantitative Positron Emission Tomography of Human Epidermal Growth Factor Receptor 2
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DOI：
10.1021/jm900420c
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发表时间：
2009-10-08
影响因子：
7.3
通讯作者：
Marik, Jan
中科院分区：
文献类型：
--
作者：
Gill, Herman S.;Tinianow, Jeff N.;Marik, Jan
基因工程产生的受体特异性蛋白作为PET显像剂很有吸引力，但由于合成时间长、放射化学收率低、特异性活性低，用传统的基于f -18的假体基进行标记存在问题。因此，我们开发了一个模块化平台，用于快速制备能够有效地将F-18引入蛋白质的水溶性假体基团。巯基特异性假体[F-18]FPEGMA证明了该平台的实用性，f -18-曲妥珠单抗- thiofab在82分钟内产生位点特异性f -18标记蛋白（f -18-曲妥珠单抗- thiofab），总放射化学产率为13 +/- 3%，特异性活性为2.2 +/- 0.2 Ci/mu mol。f -18-曲妥珠单抗- thiofab保留了天然蛋白的生物活性，并通过微pet成像成功验证了Her2在异种移植瘤小鼠模型中的表达。Hsp90抑制剂17-（烯丙胺）-17-去甲氧基格尔达霉素。
Receptor-specific proteins produced by genetic engineering are attractive as PET imaging agents, but labeling with conventional F-18-based prosthetic groups is problematic due to long synthesis times, poor radiochemical yields, and low specific activities. Therefore, we developed a modular platform for the rapid preparation of water-soluble prosthetic groups capable of efficiently introducing F-18 into proteins. The utility of this platform is demonstrated by the thiol-specific prosthetic group, [F-18]FPEGMA, which was used to produce site-specifically F-18-labeled protein (F-18-trastuzumab-ThioFab) in 82 min with a total radiochemical yield of 13 +/- 3% and a specific activity of 2.2 +/- 0.2 Ci/mu mol. F-18-trastuzumab-ThioFab retained the biological activity of native protein and was successfully validated in vivo with microPET imaging of Her2 expression in a xenograft tumor-bearing murine model modulated by. the Hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin.