Ebrahimi Aida, Pirali Hamedani Morteza, Mohammadzadeh Pardis, Safari Mostafa, Esmaeil Sadat Ebrahimi Seyed, Seyed Hamzeh Mohammad, Shafiee Ardestani Mehdi, Masoumeh Ghoreishi Seyedeh
Department of Radiopharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Department of Pharmaceutics & Medical Nanotechnology, Branch of Pharmaceutical Sciences, Islamic Azad University, Tehran, Iran.
Bioorg Chem. 2022 Nov;128:106085. doi: 10.1016/j.bioorg.2022.106085. Epub 2022 Aug 8.
Since breast cancer is the commonly cause of death among women around the world, diagnosis at the early stages is significantly important to prevent the metastasis of the cancer. Among the various growth factors that are involved in angiogenesis, vascular endothelial growth factor (VEGF) is believed to be the most important factor. Overexpressed VEGF receptor on tumors surface, is particularly interesting for cancer cells targeting purposes. In this study, citric acid dendrimer conjugated with VEGF antagonist peptide was synthesized. The obtained product was confirmed by FT-IR, TEM, DLS, and EDS. In vitro cytotoxicity assay showed no toxicity on normal cells and indicated the notably dose-dependence toxicity on cancer cells. Box-Behnken software as a computational method was used to determine the optimum amount of radiolabeling parameters. Optimized parameters for reducing agent, dendrimer-anti-VEGF, and time were 1.4 mg, 17.5 mg, and about 30 min respectively. Radiochemical purity of radio-labeled conjugated dendrimer was determined about 90 percent. SPECT imaging was done to observe the in vivo accumulation of dendrimer-anti-VEGF in the tumor site. Images showed high accumulation of radio-tracer in the tumor region. All in all, obtained results confirmed our hypothesis that the dendrimer-anti-VEGF can be a good radio-tracer for diagnosis of cancer.
由于乳腺癌是全球女性常见的死因,早期诊断对于预防癌症转移至关重要。在参与血管生成的各种生长因子中,血管内皮生长因子(VEGF)被认为是最重要的因素。肿瘤表面VEGF受体的过度表达,对于癌细胞靶向目的而言特别有趣。在本研究中,合成了与VEGF拮抗剂肽缀合的柠檬酸树枝状大分子。通过傅里叶变换红外光谱(FT-IR)、透射电子显微镜(TEM)、动态光散射(DLS)和能谱仪(EDS)对所得产物进行了确认。体外细胞毒性试验表明对正常细胞无毒性,并表明对癌细胞具有显著的剂量依赖性毒性。使用Box-Behnken软件作为一种计算方法来确定放射性标记参数的最佳量。还原剂、树枝状大分子-抗VEGF和时间的优化参数分别为1.4毫克、17.5毫克和约30分钟。放射性标记的缀合树枝状大分子的放射化学纯度测定约为90%。进行单光子发射计算机断层扫描(SPECT)成像以观察树枝状大分子-抗VEGF在肿瘤部位的体内蓄积情况。图像显示放射性示踪剂在肿瘤区域有高度蓄积。总而言之,所得结果证实了我们的假设,即树枝状大分子-抗VEGF可以成为一种用于癌症诊断的良好放射性示踪剂。