Axl-targeted cancer imaging with humanized antibody h173.
Axl-targeted cancer imaging with humanized antibody h173.
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DOI：
10.1007/s11307-013-0714-z
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发表时间：
2014-08
影响因子：
3.1
通讯作者：
Conti, Peter S.
中科院分区：
文献类型：
--
作者：
Li, Dan;Liu, Shuanglong;Liu, Ren;Park, Ryan;Yu, Haiyang;Krasnoperov, Valery;Gill, Parkash S.;Li, Zibo;Shan, Hong;Conti, Peter S.
酪氨酸激酶受体 Axl 在各种类型的癌症中过度表达，并与癌症恶性肿瘤相关。选择性 Axl 阻断可减少肿瘤生长和转移。本研究的目的是检验用近红外荧光（NIRF）染料Cy5.5标记的人源化抗Axl抗体人源化173（h173）是否可以用作肿瘤模型中Axl表达的NIRF成像的分子成像探针。 NIRF 染料 Cy5.5 通过氨基与 h173 或人正常免疫球蛋白 G (hIgG) 对照缀合。通过体内 NIRF 成像在 A549（Axl 阳性）和 NCI-H249（Axl 阴性）肺癌异种移植物中评估所得探针。还进行了离体成像和探针分布测定以确认体内成像结果。缀合后，h173-Cy5.5的结合活性测定为未修饰的h173的97.75%±2.09%。体外荧光激活细胞分选 (FACS) 和荧光显微镜分析验证了 h173 与 Axl 阳性 A549 细胞的特异性结合。然后将h173-Cy5.5应用于体内Axl表达成像。在A549（Axl阳性）癌症异种移植物中，在晚期时间点（1、2、3、4和7天），h173-Cy5.5的肿瘤摄取显着高于hIgG-Cy5.5对照（P<0.05）。相反，在NCI-H249（Axl阴性）癌症异种移植物中，hIgG-Cy5.5和h173-Cy5.5的肿瘤摄取均较低，并且在所有检查时间点均未显示出显着差异（P>0.05）。离体成像和免疫荧光染色分析进一步验证了体内成像结果。总的来说，所有体外、体内和离体数据表明 h173-Cy5.5 可以作为 Axl 靶向癌症成像的有效探针，从而有助于肿瘤诊断、预后和治疗监测。
The tyrosine kinase receptor Axl is overexpressed in various types of cancer and correlated with cancer malignancy. Selective Axl blockade reduces tumor growth and metastasis. The purpose of this study was to examine whether the humanized anti-Axl antibody humanized 173 (h173) labeled with near-infrared fluorescence (NIRF) dye Cy5.5 could be applied as a molecular imaging probe for NIRF imaging of Axl expression in tumor models. NIRF dye Cy5.5 was conjugated to h173 or human normal immunoglobulin G (hIgG) control through amino groups. The resulting probes were evaluated in both A549 (Axl positive) and NCI-H249 (Axl negative) lung cancer xenografts through in vivo NIRF imaging. Ex vivo imaging and probe distribution assay were also carried out to confirm the in vivo imaging results. After conjugation, binding activity of h173-Cy5.5 was determined to be 97.75 %± 2.09 % of the unmodified h173. In vitro fluorescence-activated cell sorting (FACS) and fluorescence microscopy analysis validated the specific binding of h173 toward Axl-positive A549 cells. h173-Cy5.5 was then applied to image Axl expression in vivo. In A549 (Axl positive) cancer xenografts, the tumor uptake of h173-Cy5.5 was significantly higher than that of the hIgG-Cy5.5 control (P<0.05) at late time points (1, 2, 3, 4, and 7 days). On the contrary, in NCI-H249 (Axl negative) cancer xenografts, the tumor uptake of both hIgG-Cy5.5 and h173-Cy5.5 was low and showed no significant difference (P>0.05) at all time points examined. Ex vivo imaging and immunofluorescence staining analysis further validated the in vivo imaging results. Collectively, all in vitro, in vivo, and ex vivo data suggested that h173-Cy5.5 could serve as a valid probe for Axl-targeted cancer imaging, which could therefore aid in tumor diagnosis, prognosis, and treatment monitoring.
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影响因子：
2.4
作者：
Song H;Sgouros G
通讯作者：
Sgouros G
DOI：
10.1073/pnas.85.6.1952
发表时间：
1988-03-01
影响因子：
11.1
作者：
LIU, E;HJELLE, B;BISHOP, JM
通讯作者：
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影响因子：
64.8
作者：
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通讯作者：
YAMANE, HK
影响因子：
4
作者：
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通讯作者：
Yokota, J
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影响因子：
3.1
作者：
Liu, Shuanglong;Li, Dan;Conti, Peter S.
通讯作者：
Conti, Peter S.