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 (⁶⁸Ga-DOTA-(Ser)₃-LTVSPWY) was developed for imaging HER2 expression in tumors. The DOTA-(Ser)₃-LTVSPWY was labeled with ⁶⁸Ga 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 ⁶⁸Ga-DOTA-(Ser)₃-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_d and B_max values for radiolabeled peptide were obtained at 2.5 ± 0.6 nM and (3.4 ± 0.2)×10⁵ 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 ⁶⁸Ga-DOTA-(Ser)₃-LTVSPWY peptide in HER2-positive tumors and the suitability of its application as a PET probe for the diagnosis of HER2-overexpression tumor.

人类表皮生长因子受体 2 (HER2) 过表达作为一种预测性生物标志物，与更多的肿瘤侵袭性和更差的癌症临床结果相关，而它的准确识别导致许多患者选择了有效的治疗方法。在这项研究中，开发了一种基于肽的 PET 探针 ( ⁶⁸ Ga-DOTA-(Ser) ₃ -LTVSPWY)，用于对肿瘤中的 HER2 表达进行成像。DOTA-(Ser) ₃ -LTVSPWY 用⁶⁸ Ga标记，然后用 HER2 阳性 SKOV-3 细胞系进行体外评估；此外，在异种移植的荷瘤裸鼠中进行了体内生物分布和 PET/CT 成像。的⁶⁸ Ga的DOTA-（SER）₃-LTVSPWY 在生理盐水和人血清中显示出大于 95% 的高放射化学纯度和良好的稳定性。细胞结合实验表明，非标记肽可以有效阻断HER2阳性卵巢癌细胞的细胞摄取。放射性标记肽的K _d和B _max值分别在2.5 ± 0.6 nM和(3.4 ± 0.2)×10 ^{5 个}位点/细胞处获得。生物分布研究表明，在注射放射性标记肽后 120 分钟，肿瘤与血液和肿瘤与肌肉的比率分别约为 1.73±0.36 和 3.78±0.17。在动物模型中注射后 60 分钟，PET/CT 的肿瘤成像显示出高对比度的肿瘤图像。因此，结果表明特定的积累⁶⁸ Ga-DOTA-(Ser) ₃ -LTVSPWY 肽在 HER2 阳性肿瘤中的应用及其作为 PET 探针用于诊断 HER2 过表达肿瘤的适用性。