Changes in HER2 expression in breast cancer xenografts after therapy can be quantified using PET and (18)F-labeled affibody molecules.
Changes in HER2 expression in breast cancer xenografts after therapy can be quantified using PET and (18)F-labeled affibody molecules.
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DOI：
10.2967/jnumed.108.057695
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发表时间：
2009-07
期刊：
影响因子：
--
通讯作者：
Capala J
中科院分区：
文献类型：
--
作者：
Kramer-Marek G;Kiesewetter DO;Capala J
HER2表达的体内成像可以直接评估肿瘤组织中的HER2状态，并提供量化HER2靶向治疗后受体表达变化的方法。这项工作描述了 HER2 特异性 18F-FBEM-ZHER2:342–Affibody 分子的体内表征及其应用，通过 PET 成像研究 17-DMAG 对 HER2 表达的影响。为了评估 PET 观察到的信号与受体表达的相关性，将示踪剂给予具有不同 HER2 表达水平的皮下人类乳腺癌异种移植物的无胸腺裸鼠。为了研究 HER2 的下调，小鼠接受了四剂量 (40 mg/kg) 17-DMAG 治疗，17-DMAG 是一种 Hsp90 抑制剂，已知可以降低 HER2 表达。在治疗之前和之后对动物进行扫描。最后一次扫描后，小鼠被安乐死，肿瘤被冷冻以进行受体分析。示踪剂很快从血液和正常组织中消除，注射后 20 分钟即可提供较高的肿瘤/血液和肿瘤/肌肉比率。记录 BT474 和 MCF7/clone18 肿瘤的正常组织和肿瘤组织之间的高对比度图像。 MCF7 肿瘤的摄取非常低，但仍可检测到，而 MDA-MB-468 则没有观察到摄取。该信号与通过免疫组织化学以及蛋白质印迹和 ELISA 评估的受体表达相关。通过治疗后 PET 成像估计，对于 BT474 和 MCF7/clone18 荷瘤小鼠，HER2 表达水平分别下降 71% (p < 4 × 10−6) 和 33% (p < 0.002)。这些变化通过生物分布研究、ELISA 和蛋白质印迹得到证实。我们的结果表明，所描述的 18F-FBEM-ZHER2:342-Affibody 分子可用于通过 PET 成像评估体内 HER2 表达，并监测受体表达响应治疗干预的可能变化。
In vivo imaging of HER2 expression may allow direct assessment of HER2 status in tumor tissue and provide means to quantify changes in receptor expression following HER2-targeted therapies. This work describes in vivo characterization of HER2-specific 18F-FBEM-ZHER2:342–Affibody molecule and its application to study the effect of 17-DMAG on HER2 expression by PET imaging. To assess the correlation of signal observed by PET with receptor expression, the tracer was administered to athymic nude mice bearing subcutaneous human breast cancer xenografts with different levels of HER2 expression. To study the down-regulation of HER2, mice were treated with four doses (40 mg/kg) of 17-DMAG, an inhibitor of Hsp90, known to decrease the HER2 expression. Animals were scanned before and after the treatment. After the last scan, mice were euthanized and tumors were frozen for receptor analysis. The tracer was eliminated quickly from the blood and normal tissues, providing high tumor/blood and tumor/muscle ratios as early as 20 min post injection. The high contrast images between normal and tumor tissue were recorded for BT474 and MCF7/clone18 tumors. Very low but still detectable uptake was observed for MCF7 tumors and none for MDA-MB-468. The signal correlated with the receptor expression assessed by immunohistochemistry as well as western blot and ELISA. The levels of HER2 expression, estimated by post-treatment PET imaging, decreased 71% (p < 4 × 10−6) and 33% (p < 0.002), respectively, for BT474- and MCF7/clone18-tumor bearing mice. These changes were confirmed by the biodistribution studies, ELISA and western blot. Our results suggest that the described 18F-FBEM-ZHER2:342–Affibody molecule can be used to assess HER2 expression in vivo by PET imaging and monitor possible changes of receptor expression in response to therapeutic interventions.
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影响因子：
1.9
作者：
Kiesewetter, Dale O.;Kramer-Marek, Gabriela;Ma, Ying;Capala, Jacek
通讯作者：
Capala, Jacek
DOI：
10.1007/s00259-008-0923-x
发表时间：
2009-01-01
影响因子：
9.1
作者：
McLarty, Kristin;Cornelissen, Bart;Reilly, Raymond M.
通讯作者：
Reilly, Raymond M.
影响因子：
7.5
作者：
Dowsett, Mitch;Hanna, Wedad M.;van de Vijver, Marc J.
通讯作者：
van de Vijver, Marc J.
影响因子：
11.2
作者：
Robinson, MK;Doss, M;Adams, GP
通讯作者：
Adams, GP
影响因子：
4.4
作者：
Friedlander, Elza;Barok, Mark;Vereb, Gyoergy
通讯作者：
Vereb, Gyoergy