Department of Radiopharmacy, Faculty of Pharmacy, Pharmaceutical Sciences Research Center, Mazandaran University of Medical Sciences, Sari, Iran; Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran.
Bioorg Chem. 2021 Jan;106:104474. doi: 10.1016/j.bioorg.2020.104474. Epub 2020 Nov 13.
Human epidermal growth factor receptor 2 (HER2) overexpression, as a predictive biomarker, is associated with more tumor aggressiveness and worse clinical outcomes in cancer, whereas it's accurate identification has led to the choice of effective treatments in many patients. In this study, a peptide-based PET probe (Ga-DOTA-(Ser)-LTVSPWY) was developed for imaging HER2 expression in tumors. The DOTA-(Ser)-LTVSPWY was labeled with Ga and then was evaluated in vitro with HER2-positive SKOV-3 cell line; moreover, the in vivo biodistribution and PET/CT imaging were performed in xenografted tumor-bearing nude mice. The Ga-DOTA-(Ser)-LTVSPWY displayed the high radiochemical purity greater than 95% and good stability in normal saline and human serum. The cellular binding experiments showed that the cell uptake in HER2-positive ovarian cancer cells could be effectively blocked by non-labeled peptide. The K and B values for radiolabeled peptide were obtained at 2.5 ± 0.6 nM and (3.4 ± 0.2) × 10 sites per cell, respectively. Biodistribution study demonstrated that tumor-to-blood and tumor-to-muscle ratios were about 1.73 ± 0.36 and 3.78 ± 0.17 at 120 min after the injection of the radiolabeled peptide, respectively. Tumor imaging by PET/CT exhibited high contrast tumor image at 60 min after injection in animal models. Consequently, the results were indicative of the specific accumulation of Ga-DOTA-(Ser)-LTVSPWY peptide in HER2-positive tumors and the suitability of its application as a PET probe for the diagnosis of HER2-overexpression tumor.
人表皮生长因子受体 2（HER2）过表达作为一种预测性生物标志物，与癌症中肿瘤侵袭性更强和临床结局更差相关，而其准确识别导致了许多患者选择有效治疗。在这项研究中，开发了一种基于肽的 PET 探针（Ga-DOTA-（Ser）-LTVSPWY）用于成像肿瘤中的 HER2 表达。DOTA-（Ser）-LTVSPWY 用 Ga 标记，然后在 HER2 阳性 SKOV-3 细胞系中进行体外评估；此外，在荷瘤裸鼠中进行了体内生物分布和 PET/CT 成像。Ga-DOTA-（Ser）-LTVSPWY 显示出大于 95%的高放射化学纯度和在生理盐水和人血清中的良好稳定性。细胞结合实验表明，非标记肽可有效阻断 HER2 阳性卵巢癌细胞的细胞摄取。放射性标记肽的 K 和 B 值分别为 2.5±0.6 nM 和（3.4±0.2）×10 个/细胞。生物分布研究表明，放射性标记肽注射后 120 分钟，肿瘤与血液和肿瘤与肌肉的比值分别约为 1.73±0.36 和 3.78±0.17。在动物模型中，注射放射性标记肽后 60 分钟进行的 PET/CT 肿瘤成像显示出高对比度的肿瘤图像。因此，结果表明 Ga-DOTA-（Ser）-LTVSPWY 肽在 HER2 阳性肿瘤中的特异性积累，适合作为用于诊断 HER2 过表达肿瘤的 PET 探针。
