Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer: Synthesis and Evaluation In Vitro and In Vivo.
Delta-Opioid Receptor (δOR) Targeted Near-Infrared Fluorescent Agent for Imaging of Lung Cancer: Synthesis and Evaluation In Vitro and In Vivo.
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DOI：
10.1021/acs.bioconjchem.5b00516
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发表时间：
2016-02-17
影响因子：
4.7
通讯作者：
Morse DL
中科院分区：
文献类型：
--
作者：
Cohen AS;Patek R;Enkemann SA;Johnson JO;Chen T;Toloza E;Vagner J;Morse DL
在美国，肺癌是癌症死亡的主要原因，在所有类型的癌症中每年新发病例数位居第二。需要更好的方法或工具来诊断和治疗这种疾病，以改善患者的治疗结果。据报道，δ阿片受体（δOR）在肺癌中过度表达，而在正常肺中不表达。因此，我们决定开发一种针对该受体的肺癌特异性显像剂。我们之前开发了一种基于与 Cy5 荧光染料缀合的合成肽拮抗剂 (Dmt-Tic) 的 δOR 靶向荧光成像剂。在这项工作中，我们描述了与较长波长近红外荧光 (NIRF) 染料 Li-cor IR800CW 缀合的 Dmt-Tic 的合成。在设计用于过表达 δOR 的细胞中，使用镧系元素时间分辨荧光 (LTRF) 竞争性结合测定法研究了 Dmt-Tic-IR800 对 δOR 的结合亲和力。此外，我们还鉴定了具有高和低内源性 δOR 表达的肺癌细胞系。我们使用共聚焦荧光显微镜成像证实了这些细胞系中的蛋白质表达，并使用该技术来估计内源表达肺癌细胞系中的细胞表面受体数量。使用工程细胞系和小鼠皮下异种移植模型中的内源表达肺癌细胞显示了 Dmt-Tic-IR800 对 δOR 体内成像的选择性。总之，本研究开发的 δOR 特异性荧光探针在肺癌成像方面显示出良好的潜力。
In the United States, lung cancer is the leading cause of cancer deaths and ranks second in the number of new cases annually among all types of cancers. Better methods or tools for diagnosing and treating this disease are needed to improve patient outcomes. The delta opioid receptor (δOR) is reported to be overexpressed in lung cancers and not expressed in normal lung. Thus, we decided to develop a lung cancer-specific imaging agent targeting this receptor. We have previously developed a δOR–targeted fluorescent imaging agent based on a synthetic peptide antagonist (Dmt-Tic) conjugated to a Cy5 fluorescent dye. In this work, we describe the synthesis of Dmt-Tic conjugated to a longer wavelength near-infrared fluorescent (NIRF) dye, Li-cor IR800CW. Binding affinity of Dmt-Tic-IR800 for the δOR was studied using lanthanide time-resolved fluorescence (LTRF) competitive binding assays in cells engineered to overexpress the δOR. In addition, we identified lung cancer cell lines with high- and low-endogenous expression of the δOR. We confirmed protein expression in these cell lines using confocal fluorescence microscopy imaging and used this technique to estimate the cell-surface receptor number in the endogenously expressing lung cancer cell lines. The selectivity of Dmt-Tic-IR800 for imaging of the δOR in vivo was shown using both engineered cell lines and endogenously expressing lung cancer cells in subcutaneous xenograft models in mice. In conclusion, the δOR–specific fluorescent probe developed in this study displays excellent potential for imaging of lung cancer.
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影响因子：
16.6
作者：
Asanuma D;Sakabe M;Kamiya M;Yamamoto K;Hiratake J;Ogawa M;Kosaka N;Choyke PL;Nagano T;Kobayashi H;Urano Y
通讯作者：
Urano Y
影响因子：
3.1
作者：
Keereweer, Stijn;Kerrebijn, Jeroen D. F.;van Driel, Pieter B. A. A.;Xie, Bangwen;Kaijzel, Eric L.;Snoeks, Thomas J. A.;Que, Ivo;Hutteman, Merlijn;van der Vorst, Joost R.;Mieog, J. Sven D.;Vahrmeijer, Alexander L.;van de Velde, Cornelis J. H.;de Jong, Robert J. Baatenburg;Lowik, Clemens W. G. M.
通讯作者：
Lowik, Clemens W. G. M.
影响因子：
3.1
作者：
Collier, TL;Schiller, PW;Waterhouse, RN
通讯作者：
Waterhouse, RN
影响因子：
7.3
作者：
Amanda Shanks Huynh;Chung, Woo Jin;Vagner, Josef
通讯作者：
Vagner, Josef
影响因子：
2.8
作者：
Black, Kvar C.;Kirkpatrick, Nathaniel D.;Romanowski, Marek
通讯作者：
Romanowski, Marek