Using in vivo fluorescence lifetime imaging to detect HER2-positive tumors.
Using in vivo fluorescence lifetime imaging to detect HER2-positive tumors.
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DOI：
10.1186/s13550-018-0384-6
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发表时间：
2018-04-04
期刊：
影响因子：
3.2
通讯作者：
Gandjbakhche AH
中科院分区：
文献类型：
--
作者：
Ardeshirpour Y;Sackett DL;Knutson JR;Gandjbakhche AH
评估个体患者肿瘤生物标志物的状态将有助于个性化治疗策略，持续监测这些生物标志物及其与治疗药物的结合过程将为早期评估治疗干预的效果提供一种手段。由于肿瘤血管化的渗漏，荧光探针可以在肿瘤区域内积累，这使得很难区分测量的荧光强度是来自与靶受体结合的探针还是仅仅积累在肿瘤内部的未结合探针。在本文中，我们研究了荧光寿命作为一种手段来区分结合的HER2特异性粘附体探针与HER2受体。我们的成像系统是一个时间分辨荧光系统，使用钛蓝宝石飞秒脉冲激光作为光源，时间相关单光子计数（TCSPC）系统作为检测器，用于计算造影剂的寿命。HER2特异性修饰体（his6 - zer2:GS-Cys） （affbody, Stockholm, Sweden）与Dylight750荧光探针（thermofisher - scientific, Waltham, Massachusetts）结合作为造影剂，6种已知表达不同水平HER2/neu的人类癌细胞系BT-474、skv -3、NCI-N87、MDA-MB-361、MCF-7和MDA-MB-468用于胸腺小鼠异种移植。通过比较未结合造影剂（对侧部位）的寿命与肿瘤部位的荧光寿命，我们的结果表明，随着HER2特异性粘附体探针与肿瘤受体的结合，荧光寿命减少。在HER2中高表达的肿瘤中，肿瘤荧光寿命降低约15% （100ps）。在HER2受体水平低的肿瘤中观察到较小的下降，而在非HER2受体表达的肿瘤中没有观察到变化。使用与Dylight750荧光探针结合的HER2特异性附着体作为造影剂，我们在活体动物中证明，结合造影剂的荧光寿命变化可用于仅一次测量体内表达HER2的肿瘤的高至中水平表达。其基本原理是，我们的特定探针的荧光寿命是敏感的亲和力，并与其他分子的特定相互作用。
Assessment of the status of tumor biomarkers in individual patients would facilitate personalizing treatment strategy, and continuous monitoring of those biomarkers and their binding process to the therapeutic drugs would provide a means for early evaluation of the efficacy of therapeutic intervention. Fluorescent probes can accumulate inside the tumor region due to the leakiness of its vascularization and this can make it difficult to distinguish if the measured fluorescence intensity is from probes bound to target receptors or just accumulated unbound probes inside the tumor. In this paper, we have studied the fluorescence lifetime as a means to distinguish bound HER2 specific affibody probes to HER2 receptors. Our imaging system is a time-resolved fluorescence system using a Ti-Sapphire femtosecond pulse laser as source and Time correlated Single photon Counting (TCSPC) system as detector for calculating the lifetime of the contrast agent. HER2-specific Affibody (His6-ZHER2:GS-Cys) (Affibody, Stockholm, Sweden) conjugated with a Dylight750 fluorescent probe (Thermo-Fisher-Scientific, Waltham, Massachusetts) was used as contrast agent and six human cancer cell lines, BT-474, SKOV-3, NCI-N87, MDA-MB-361, MCF-7, and MDA-MB-468, known to express different levels of HER2/neu, are used in athymic mice xenografts. By comparing the lifetime of unbound contrast agent (at the contralateral site) to the fluorescence lifetime at the tumor site, our results show that the fluorescence lifetime decreases as HER2 specific Affibody probes bind to the tumor receptors. A decrease of ~15% (100ps) in tumor fluorescence lifetime was observed in tumors with mid to high HER2 expression. Smaller decreases were observed in tumors with low-level of HER2 receptors and no change was observed in the non-HER2-expressing tumors. Using HER2-specific Affibody conjugated with the Dylight750 fluorescent probe as contrast agent, we demonstrated in live animals that change in fluorescence lifetime of the bound contrast agent can be used to assess the high to mid-level expression of HER2 expressing tumors in-vivo in only one measurement. The rationale is that the fluorescence lifetime of our specific probe is sensitive to affinity to, and specific interaction with, other molecules.
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影响因子：
2.4
作者：
Chernomordik, Victor;Gandjbakhche, Amir H.;Hassan, Moinuddin;Pajevic, Sinisa;Weiss, George H.
通讯作者：
Weiss, George H.
DOI：
10.2217/nnm.12.12
发表时间：
2012-03
期刊：
Nanomedicine (London, England)
影响因子：
--
作者：
Hellebust A;Richards-Kortum R
通讯作者：
Richards-Kortum R
影响因子：
2.8
作者：
Chernomordik, Victor;Hassan, Moinuddin;Capala, Jacek
通讯作者：
Capala, Jacek
影响因子：
3.5
作者：
Pogue, Brian W.;Samkoe, Kimberley S.;Hasan, Tayyaba
通讯作者：
Hasan, Tayyaba
影响因子：
3.5
作者：
Yarden, Y
通讯作者：
Yarden, Y