Currently, most patients with non–small cell lung cancer (NSCLC) are diagnosed in advanced stages with a poor five-year survival rate. Therefore, intensive research aimed at finding novel therapeutic strategies has been ongoing; experimental models that reliably emulate NSCLC disease are greatly needed to predict responses to novel therapeutics. Therefore, we developed patient-derived xenograft (PDX) models of NSCLC, which we then used to evaluate the therapeutic efficacy of 177Lu-EB-RGD, a peptide-based radiopharmaceutical with improved pharmacokinetics that targets integrin αvβ3. In this study, three different groups of NSCLC-PDXs were successfully established, all of which maintained the same IHC and genetic characteristics of the human primary tumor. The two NSCLC-PDX groups with intense and low expression of integrin αvβ3 (denoted as PDXαvβ3+ and PDXαvβ3-) were chosen as the experimental models to evaluate the in vivo biological behavior of 177Lu-EB-RGD. In SPECT imaging and biodistribution studies, 177Lu-EB-RGD showed significantly higher accumulation in PDXαvβ3+ and PDXαvβ3- models than its corresponding monomer 177Lu-RGD. A single dose of 18.5 MBq 177Lu-EB-RGD was enough to completely eradicate the tumors in PDXαvβ3+, with no sign of tumor recurrence during the observation period. Such treatment was also efficacious in PDXαvβ3-: a single dose of 29.6 MBq 177Lu-EB-RGD led to a significant delay in tumor growth as compared with that in the control or 177Lu-RGD group. The preclinical data from the use of this model suggest that 177Lu-EB-RGD may be an effective treatment option for NSCLC and should be further evaluated in human trials.

中文翻译：

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使用 177Lu-EB-RGD 在患者来源的异种移植物中靶向放射性核素治疗

目前，大多数非小细胞肺癌（NSCLC）患者被诊断为晚期，五年生存率很低。因此，旨在寻找新治疗策略的深入研究一直在进行。非常需要可靠地模拟 NSCLC 疾病的实验模型来预测对新疗法的反应。因此，我们开发了 NSCLC 的患者来源的异种移植 (PDX) 模型，然后我们将其用于评估 177Lu-EB-RGD 的治疗效果，177Lu-EB-RGD 是一种基于肽的放射性药物，具有改善的药代动力学，靶向整合素 αvβ3。在这项研究中，成功​​建立了三组不同的NSCLC-PDXs，它们都保持了与人类原发肿瘤相同的IHC和遗传特征。选择整合素αvβ3高低表达的两个NSCLC-PDX组（分别表示为PDXαvβ3+和PDXαvβ3-）作为实验模型，评估177Lu-EB-RGD的体内生物学行为。在 SPECT 成像和生物分布研究中，177Lu-EB-RGD 在 PDXαvβ3+ 和 PDXαvβ3- 模型中的积累明显高于其相应的单体 177Lu-RGD。单剂量 18.5 MBq 177Lu-EB-RGD 足以完全根除 PDXαvβ3+ 中的肿瘤，在观察期间没有肿瘤复发的迹象。这种治疗在 PDXαvβ3- 中也有效：与对照组或 177Lu-RGD 组相比，单剂量 29.6 MBq 177Lu-EB-RGD 导致肿瘤生长显着延迟。