Department of Organic Chemistry, Faculty of Science, Palacky University, 77900 Olomouc, Czech Republic.
Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University, 77900 Olomouc, Czech Republic.
Int J Mol Sci. 2021 Jul 9;22(14):7391. doi: 10.3390/ijms22147391.
Angiogenesis has a pivotal role in tumor growth and the metastatic process. Molecular imaging was shown to be useful for imaging of tumor-induced angiogenesis. A great variety of radiolabeled peptides have been developed to target αvβ3 integrin, a target structure involved in the tumor-induced angiogenic process. The presented study aimed to synthesize deferoxamine (DFO)-based c(RGD) peptide conjugate for radiolabeling with gallium-68 and perform its basic preclinical characterization including testing of its tumor-imaging potential. DFO-c(RGDyK) was labeled with gallium-68 with high radiochemical purity. In vitro characterization including stability, partition coefficient, protein binding determination, tumor cell uptake assays, and ex vivo biodistribution as well as PET/CT imaging was performed. [Ga]Ga-DFO-c(RGDyK) showed hydrophilic properties, high stability in PBS and human serum, and specific uptake in U-87 MG and M21 tumor cell lines in vitro and in vivo. We have shown here that [Ga]Ga-DFO-c(RGDyK) can be used for αvβ3 integrin targeting, allowing imaging of tumor-induced angiogenesis by positron emission tomography.
血管生成在肿瘤生长和转移过程中起着关键作用。分子成像已被证明可用于肿瘤诱导的血管生成成像。已经开发了大量放射性标记的肽来靶向αvβ3 整联蛋白，这是参与肿瘤诱导的血管生成过程的靶结构。本研究旨在合成基于去铁胺（DFO）的 c（RGD）肽缀合物，用于用镓-68 标记，并对其进行基本的临床前特性分析，包括测试其肿瘤成像潜力。DFO-c（RGDyK）用镓-68 标记，具有高放射化学纯度。进行了体外特性分析，包括稳定性、分配系数、蛋白质结合测定、肿瘤细胞摄取测定以及体外和体内的生物分布以及 PET/CT 成像。[Ga]Ga-DFO-c（RGDyK）表现出亲水性、在 PBS 和人血清中的高稳定性以及在 U-87 MG 和 M21 肿瘤细胞系中的特异性摄取。我们在这里表明，[Ga]Ga-DFO-c（RGDyK）可用于靶向αvβ3 整联蛋白，允许通过正电子发射断层扫描成像来检测肿瘤诱导的血管生成。
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