Radiopharmacy Center, Institute of Energy and Nuclear Research, Av. Prof. Lineu Prestes, 2242, São Paulo, 05508-000, Brazil.
School of Pharmaceutical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes, 580 Bloco 17, São Paulo, SP, 05508-900, Brazil.
Appl Biochem Biotechnol. 2018 Aug;185(4):863-874. doi: 10.1007/s12010-018-2700-z. Epub 2018 Jan 24.
Early and accurate detection of primary or metastatic tumors is of great value in staging, treatment management, and prognosis. Tumor angiogenesis plays an essential role in the growth, invasion, and metastatic spread of solid cancers, and so, is a promising approach for tumor imaging. The GX1 (CGNSNPKSC) peptide was identified by phage display library and has been investigated as a marker for human cancers. This study aims to evaluate the Tc-HYNIC-PEG-c (GX1) as a biomarker for tumor imaging. Our results showed that GX1 specifically binds to tumor cells in vitro. SKMEL28 and MDA-MB231 cells achieved total binding peak at 60 min of incubation. For B16F10 and MKN45 cells, the total and specific binding were similar during all time points, while A549 cell line showed rapid cellular total uptake of the tracer at 30 min of incubation. Biodistribution showed low non-specific uptakes and rapid renal excretion. Melanoma tumors showed enhanced GX1 uptake in animal model at 60 min, and it was significantly blocked by cold peptide. The radiotracer showed tumor specificity, especially in melanomas that are highly vascularized tumors. In this sense, it should be considered in future studies, aiming to evaluate degree of angiogenesis, progression, and invasion of tumors.
早期和准确地检测原发性或转移性肿瘤对于分期、治疗管理和预后具有重要价值。肿瘤血管生成在实体瘤的生长、侵袭和转移扩散中起着至关重要的作用，因此，是肿瘤成像的一种有前途的方法。GX1（CGNSNPKSC）肽是通过噬菌体展示文库鉴定的，已被研究作为人类癌症的标志物。本研究旨在评估 Tc-HYNIC-PEG-c（GX1）作为肿瘤成像的生物标志物。我们的结果表明，GX1 在体外特异性结合肿瘤细胞。在孵育 60 分钟时，SKMEL28 和 MDA-MB231 细胞达到总结合峰。对于 B16F10 和 MKN45 细胞，在所有时间点，总结合和特异性结合相似，而 A549 细胞系在孵育 30 分钟时显示出放射性示踪剂的快速细胞总摄取。生物分布显示低非特异性摄取和快速肾排泄。在动物模型中，黑色素瘤肿瘤在 60 分钟时显示出 GX1 摄取增加，并且被冷肽显著阻断。该放射性示踪剂显示出肿瘤特异性，特别是在高度血管化的黑色素瘤中。从这个意义上说，它应该在未来的研究中考虑，旨在评估肿瘤的血管生成、进展和侵袭程度。
