In vivo selection of phage for the optical Imaging of PC-3 human prostate carcinoma in mice
In vivo selection of phage for the optical Imaging of PC-3 human prostate carcinoma in mice
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DOI：
10.1593/neo.06331
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发表时间：
2006-09-01
期刊：
影响因子：
4.8
通讯作者：
Deutscher, Susan L.
中科院分区：
文献类型：
--
作者：
Newton, Jessica R.;Kelly, Kimberly A.;Deutscher, Susan L.
对早期和侵袭性前列腺癌的检测和空间定位的医学需求日益增加。从噬菌体（噬菌体）文库筛选中获得的亲和配体可以开发用于荧光染料光学成像的分子靶向前列腺癌。为了实现这一目标，我们使用了体内噬菌体展示和一种新描述的微计划实验来选择在严重联合免疫缺陷小鼠中外渗和结合人PC-3前列腺癌异种移植物的噬菌体。一个显示肽序列IAGLATPGWSHWLAL的噬菌体克隆（G1）用近红外荧光团AlexaFluor 680进行荧光标记，并在体外和体内评估其结合和靶向PC-3前列腺癌的能力。荧光标记的噬菌体克隆（G1）在实验中肿瘤与肌肉的比率接近30。此外，前列腺肿瘤（PC-3）很容易被光学成像方法检测到。这些结果证明了疾病特异性文库衍生荧光探针可以快速开发用于光学手段早期检测癌症的原理。
There is an increasing medical need to detect and spatially localize early and aggressive forms of prostate cancer. Affinity ligands derived from bacteriophage (phage) library screens can be developed to molecularly target prostate cancer with fluorochromes for optical imaging. Toward this goal, we used in vivo phage display and a newly described micropanning assay to select for phage that extravasate and bind human PC-3 prostate carcinoma xenografts in severe combined immune deficiency mice. One resulting phage clone (G1) displaying the peptide sequence IAGLATPGWSHWLAL was fluorescently labeled with the near-infrared fluorophore AlexaFluor 680 and was evaluated both in vitro and in vivo for its ability to bind and target PC-3 prostate carcinomas. The fluorescently labeled phage clone (G1) had a tumor-to-muscle ratio of similar to 30 in experiments. In addition, prostate tumors (PC-3) were readily detectable by optical-imaging methods. These results show proof of principle that disease-specific library-derived fluorescent probes can be rapidly developed for use in the early detection of cancers by optical means.