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使用 Sgc8-c 适体 PTK7 识别器对转移性和非转移性黑色素瘤进行成像。

Metastatic and non-metastatic melanoma imaging using Sgc8-c aptamer PTK7-recognizer.

机构信息

Área de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de La República, 11400, Montevideo, Uruguay.

Departamento de Desarrollo Biotecnológico, Instituto de Higiene, Facultad de Medicina, Universidad de La República, 11600, Montevideo, Uruguay.

出版信息

Sci Rep. 2021 Oct 7;11(1):19942. doi: 10.1038/s41598-021-98828-6.

Abstract

Melanoma is one of the most aggressive and deadly skin cancers, and although histopathological criteria are used for its prognosis, biomarkers are necessary to identify the different evolution stages. The applications of molecular imaging include the in vivo diagnosis of cancer with probes that recognize the tumor-biomarkers specific expression allowing external image acquisitions and evaluation of the biological process in quali-quantitative ways. Aptamers are oligonucleotides that recognize targets with high affinity and specificity presenting advantages that make them interesting molecular imaging probes. Sgc8-c (DNA-aptamer) selectively recognizes PTK7-receptor overexpressed in various types of tumors. Herein, Sgc8-c was evaluated, for the first time, in a metastatic melanoma model as molecular imaging probe for in vivo diagnostic, as well as in a non-metastatic melanoma model. Firstly, two probes, radio- and fluorescent-probe, were in vitro evaluated verifying the high specific PTK7 recognition and its internalization in tumor cells by the endosomal route. Secondly, in vivo proof of concept was performed in animal tumor models. In addition, they have rapid clearance from blood exhibiting excellent target (tumor)/non-target organ ratios. Furthermore, optimal biodistribution was observed 24 h after probes injections accumulating almost exclusively in the tumor tissue. Sgc8-c is a potential tool for their specific use in the early detection of melanoma.

摘要

黑色素瘤是最具侵袭性和致命性的皮肤癌之一,尽管组织病理学标准可用于其预后评估,但仍需要生物标志物来识别不同的演进阶段。分子成像的应用包括使用能够识别肿瘤标志物特异性表达的探针来进行癌症的体内诊断,从而允许进行外部图像采集,并以定性和定量的方式评估生物过程。适体是能够高亲和力和特异性识别靶标的寡核苷酸,具有使其成为有趣的分子成像探针的优势。Sgc8-c(DNA-适体)选择性地识别在各种类型的肿瘤中过表达的 PTK7 受体。在此,首次将 Sgc8-c 作为体内诊断的分子成像探针在转移性黑色素瘤模型中进行了评估,并在非转移性黑色素瘤模型中进行了评估。首先,对两种探针(放射性探针和荧光探针)进行了体外评估,证实了对 PTK7 的高特异性识别及其通过内体途径内化到肿瘤细胞中。其次,在动物肿瘤模型中进行了体内验证。此外,它们从血液中快速清除,表现出优异的靶标(肿瘤)/非靶标器官比。此外,在探针注射后 24 小时观察到最佳的生物分布,几乎仅在肿瘤组织中积累。Sgc8-c 是特异性用于黑色素瘤早期检测的潜在工具。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8763/8497559/d80eec3ad7e5/41598_2021_98828_Fig1_HTML.jpg

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