Targeting the EphB4 receptor for cancer diagnosis and therapy monitoring.
Targeting the EphB4 receptor for cancer diagnosis and therapy monitoring.
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DOI：
10.1021/mp300461b
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发表时间：
2013-01-07
影响因子：
4.9
通讯作者：
Conti PS
中科院分区：
文献类型：
--
作者：
Li D;Liu S;Liu R;Park R;Hughes L;Krasnoperov V;Gill PS;Li Z;Shan H;Conti PS
越来越多的证据表明，EphB4在多种癌症类型的癌症进展中发挥关键作用。事实上，专注于EphB4的治疗已经成为各种癌症治疗策略的潜在重要组成部分。然而，对于不同的癌症，肿瘤对EphB4抑制的敏感性可能并不一致。在这项研究中，我们基于EphB4特异性人源化单抗hAb47，开发了用于EphB4靶向成像的近红外荧光(NIRF)探针。NIRF染料Cy5.5通过与氨基(命名为hAb47-Cy5.5)或巯基(命名为hAb47-Cy5.5-MAL)反应引入到hAb47中。在HT-29异种移植和mAb131(抗EphB4)处理的模型中对所产生的探针进行了评估。虽然这些方法都导致了抗体的重链和轻链的修饰，但大多数EphB4结合亲和力仍保持不变(hAb47-Cy5.5和hAb47-Cy5.5-Mal分别为81.62±2.08%和77.14±2.46%)。然后选择hAb47-Cy5.5用于体内EphB4表达的NIRF成像。在HT29结直肠癌移植瘤中，hAb47-Cy5.5的肿瘤摄取率明显高于对照HigG-Cy5.5，免疫荧光染色进一步证实了这一点。此外，hAb47-Cy5.5使用另一种EphB4特异性抗体mAb131成功地成像了EphB4靶向免疫治疗中EphB4表达的降低(经Western印迹证实)。总的来说，hAb47-Cy5.5可以作为一种特异性的NIRF造影剂，用于EphB4表达的非侵入性成像，它可以预测单个肿瘤是否可能对EphB4靶向干预产生反应，以及监测治疗反应。
Accumulating evidence suggests that EphB4 plays key roles in cancer progression in numerous cancer types. In fact, therapies focusing on EphB4 have become potentially important components of various cancer treatment strategies. However, tumor sensitivity to EphB4 suppression may not be uniform for different cancers. In this study, we developed near-infrared fluorescence (NIRF) probes for EphB4 targeted imaging, based on EphB4-specific humanized monoclonal antibody hAb47. NIRF dye Cy5.5 was introduced to hAb47 either through the reaction with amino groups (named as hAb47-Cy5.5) or sulfhydryl groups (named as hAb47-Cy5.5-Mal). The resulting probes were evaluated in both HT-29 xenograft and the mAb131 (anti-EphB4) treated models. Although these methods lead to modifications of both the heavy chain and light chain of the antibody, the majority of the EphB4 binding affinity was maintained (81.62±2.08% for hAb47-Cy5.5 and 77.14±2.46% for hAb47-Cy5.5-Mal, respectively). hAb47-Cy5.5 was then chosen for in vivo NIRF imaging of EphB4 expression. In HT29 colorectal tumor xenografts, hAb47-Cy5.5 demonstrated significantly higher tumor uptake compared with hIgG-Cy5.5 control, which was further confirmed by immunofluorescent staining. Moreover, hAb47-Cy5.5 successfully imaged the decreased EphB4 expression (confirmed by Western blot) in EphB4-targeted immunotherapy using another EphB4-specific antibody, mAb131. Collectively, hAb47-Cy5.5 could be used as a specific NIRF contrast agent for noninvasive imaging of EphB4 expression, which may predict whether an individual tumor would likely to respond to EphB4 targeted interventions, as well as monitor the therapeutic response.
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影响因子：
5.7
作者：
Spannuth WA;Mangala LS;Stone RL;Carroll AR;Nishimura M;Shahzad MM;Lee SJ;Moreno-Smith M;Nick AM;Liu R;Jennings NB;Lin YG;Merritt WM;Coleman RL;Vivas-Mejia PE;Zhou Y;Krasnoperov V;Lopez-Berestein G;Gill PS;Sood AK
通讯作者：
Sood AK
受体酪氨酸激酶EPHB4在卵巢癌中过表达，提供生存信号并预测结果不佳。
影响因子：
8.8
作者：
Kumar, S. R.;Masood, R.;Spannuth, W. A.;Singh, J.;Scehnet, J.;Kleiber, G.;Jennings, N.;Deavers, M.;Krasnoperov, V.;Dubeau, L.;Weaver, F. A.;Sood, A. K.;Gill, P. S.
通讯作者：
Gill, P. S.
影响因子：
4.9
作者：
Hu CM;Kaushal S;Tran Cao HS;Aryal S;Sartor M;Esener S;Bouvet M;Zhang L
通讯作者：
Zhang L
影响因子：
16
作者：
Gerety, SS;Wang, HU;Anderson, DJ
通讯作者：
Anderson, DJ
使用 64Cu 标记肽对 EphB4 受体进行体内小动物 PET/CT
影响因子：
9.3
作者：
Xiong, Chiyi;Huang, Miao;Li, Chun
通讯作者：
Li, Chun