[18F]FBEM-Z(HER2:342)-Affibody molecule-a new molecular tracer for in vivo monitoring of HER2 expression by positron emission tomography.
[18F]FBEM-Z(HER2:342)-Affibody molecule-a new molecular tracer for in vivo monitoring of HER2 expression by positron emission tomography.
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DOI：
10.1007/s00259-007-0658-0
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发表时间：
2008-05
影响因子：
9.1
通讯作者：
Capala, Jacek
中科院分区：
文献类型：
--
作者：
Kramer-Marek, Gabriela;Kiesewetter, Dale O.;Martiniova, Lucia;Jagoda, Elaine;Lee, Sang Bong;Capala, Jacek
人表皮生长因子受体-2（HER 2）受体在癌症中的表达与不良预后相关。如果在体内进行评估，它可以用于为个体患者选择合适的治疗方法，并用于监测肿瘤对靶向治疗的反应。我们已经用氟-18放射性标记了HER 2结合亲和体分子，用于通过正电子发射断层扫描（PET）在体内监测HER 2表达。将HER 2结合ZHER 2：342-Cys亲和体分子与N-2-（4-[18F]氟苯甲酰氨基）乙基]马来酰亚胺（[18F]FBEM）缀合。通过受体饱和和竞争测定表征所得放射性缀合物的体外结合。对于体内研究，将放射性缀合物注射到携带皮下HER 2阳性或HER 2阴性肿瘤的小鼠的尾静脉中。一些小鼠用未标记的ZHER 2：342−Cys预处理。在注射后不同时间处死动物，并测量选定组织中的放射性。使用动物PET扫描仪获得PET图像。体外实验表明与HER 2特异性、高亲和力结合。PET成像显示，早在注射后20分钟，肿瘤中的放射性就有很高的蓄积，60分钟后达到平台期。这些结果得到了生物分布研究的证实，表明早在注射后1小时，肿瘤与血液的浓度比为7.5，4小时增加到27。用未标记的ZHER 2：342-Cys预饱和受体可将HER 2阳性肿瘤中的放射性积聚降低至HER 2阴性肿瘤中观察到的水平。我们的结果表明，[18 F] FBEM-ZHER 2：342放射性缀合物可用于评估体内HER 2表达。
The expression of human epidermal growth factor receptor-2 (HER2) receptors in cancers is correlated with a poor prognosis. If assessed in vivo, it could be used for selection of appropriate therapy for individual patients and for monitoring of the tumor response to targeted therapies. We have radiolabeled a HER2-binding Affibody molecule with fluorine-18 for in vivo monitoring of the HER2 expression by positron emission tomography (PET). The HER2-binding ZHER2:342-Cys Affibody molecule was conjugated with N-2-(4-[18F]fluorobenzamido)ethyl]maleimide ([18F]FBEM). The in vitro binding of the resulting radioconjugate was characterized by receptor saturation and competition assays. For in vivo studies, the radioconjugate was injected into the tail vein of mice bearing subcutaneous HER2-positive or HER2-negative tumors. Some of the mice were pre-treated with non-labeled ZHER2:342−Cys. The animals were sacrificed at different times post-injection, and the radioactivity in selected tissues was measured. PET images were obtained using an animal PET scanner. In vitro experiments indicated specific, high-affinity binding to HER2. PET imaging revealed a high accumulation of the radioactivity in the tumor as early as 20 min after injection, with a plateau being reached after 60 min. These results were confirmed by biodistribution studies demonstrating that, as early as 1 h post-injection, the tumor to blood concentration ratio was 7.5 and increased to 27 at 4 h. Pre-saturation of the receptors with unlabeled ZHER2:342-Cys lowered the accumulation of radioactivity in HER2-positive tumors to the levels observed in HER2-negative ones. Our results suggest that the [18F]FBEM-ZHER2:342 radioconjugate can be used to assess HER2 expression in vivo.
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影响因子：
11.5
作者：
Milenic, DE;Garmestani, K;Brechbiel, MW
通讯作者：
Brechbiel, MW
影响因子：
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作者：
De Lorenzo, C;Cozzolino, R;D'Alessio, G
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Slamon, DJ
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作者：
Kiesewetter, DO;Jagoda, EM;Eckelman, WC
通讯作者：
Eckelman, WC