Integrin α_vβ₃, a subtype of the arginine-glycine-aspartate (RGD)–recognizing cell surface integrins, is upregulated on endothelial cells during angiogenesis and on tumor cells. Because of involvement in tumor growth, invasiveness and metastases, and angiogenesis, integrin α_vβ₃ is an attractive target in cancers. In this study, we applied ⁶⁸Ga-NODAGA-E[c(RGDyK)]₂ for imaging of integrin α_vβ₃ in patients with neuroendocrine neoplasms (NENs) and its potential use for prognostication. We hypothesized that ⁶⁸Ga-NODAGA-E[c(RGDyK)]₂ PET/CT would show tumor lesion uptake and that higher tumor lesion uptake was associated with a poorer prognosis. Methods: Between December 2017 and November 2020 we prospectively enrolled 113 patients with NEN of all grades (2019 World Health Organization classification) for ⁶⁸Ga-NODAGA-E[c(RGDyK)]₂ PET/CT. The scan was acquired 45 min after injection of 200 MBq of ⁶⁸Ga-NODAGA-E[c(RGDyK)]₂. Board-certified specialists in nuclear medicine and radiology analyzed the PET/CT measuring SUV_max in tumor lesions. Positive tumor lesions were defined as those with tumor-to-liver background ≥ 2. Maximal tumor SUV_max for each patient was used as a predictor of outcome. Patients were followed for at least 1 y to assess progression-free survival and overall survival. Results: Of 113 patients enrolled in the trial, 99 underwent ⁶⁸Ga-NODAGA-E[c(RGDyK)]₂ PET/CT, with 97 patients having evaluable lesions. The patients predominantly had small intestinal (64%) or pancreatic (20%) NEN and most had metastatic disease (93%). Most patients had low-grade tumors (78%), whereas 22% had high-grade tumors. During a median follow-up of 31 mo (interquartile range, 26–38 mo), 62 patients (64%) experienced disease progression and 25 (26%) patients died. In total, 76% of patients had positive tumor lesions, and of the patients with high-grade tumors 91% had positive tumor lesions. High integrin α_vβ₃ expression, defined as an SUV_max of at least 5.25, had a hazard ratio of 2.11 (95% CI, 1.18–3.78) and 6.95 (95% CI, 1.64–29.51) for progression-free survival and overall survival, respectively (P = 0.01 for both). Conclusion: Tumor lesion uptake of ⁶⁸Ga-NODAGA-E[c(RGDyK)]₂ was evident in patients with all grades of NEN. High uptake was associated with a poorer prognosis. Further studies are warranted to establish whether ⁶⁸Ga-NODAGA-E[c(RGDyK)]₂ PET/CT may become a prediction tool for identification of patients eligible for treatments targeting integrin α_vβ_3.

整合素 α _v β ₃是精氨酸-甘氨酸-天冬氨酸 (RGD) 识别细胞表面整合素的一种亚型，在内皮细胞和肿瘤细胞上的血管生成过程中表达上调。由于参与肿瘤生长、侵袭和转移以及血管生成，整合素 α _v β ₃是癌症中一个有吸引力的靶点。在本研究中，我们应用⁶⁸ Ga-NODAGA-E[c(RGDyK)] ₂对神经内分泌肿瘤 (NEN) 患者的整合素 α _v β _{3进行成像及其在预测中的潜在用途。}我们假设⁶⁸ Ga-NODAGA-E[c(RGDyK)] ₂ PET/CT 将显示肿瘤病灶摄取，并且较高的肿瘤病灶摄取与较差的预后相关。方法： 2017 年 12 月至 2020 年 11 月期间，我们前瞻性招募了 113 名所有级别的 NEN 患者（2019 年世界卫生组织分类），进行⁶⁸ Ga-NODAGA-E[c(RGDyK)] ₂ PET/CT。^{注射200 MBq 68} Ga-NODAGA-E[c(RGDyK)] ₂后45分钟获得扫描。委员会认证的核医学和放射学专家分析了 PET/CT 测量肿瘤病变的SUV _{max 。}阳性肿瘤病变定义为肿瘤与肝脏背景≥2的病变。每位患者的最大肿瘤SUV _max被用作结果的预测因子。对患者进行至少 1 年的随访，以评估无进展生存期和总生存期。结果：在参与试验的 113 名患者中，99 名患者接受了⁶⁸ Ga-NODAGA-E[c(RGDyK)] ₂ PET/CT，其中 97 名患者存在可评估病变。患者主要患有小肠 (64%) 或胰腺 (20%) NEN，大多数患有转移性疾病 (93%)。大多数患者患有低级别肿瘤（78%），而 22% 患有高级别肿瘤。在中位随访 31 个月（四分位距，26-38 个月）期间，62 名患者 (64%) 出现疾病进展，25 名患者 (26%) 死亡。总共有 76% 的患者肿瘤病灶呈阳性，而高级别肿瘤患者中 91% 的肿瘤病灶呈阳性。高整合素 α _v β ₃表达（定义为 SUV _max至少为 5.25）无进展生存期的风险比为 2.11（95% CI，1.18–3.78）和 6.95（95% CI，1.64–29.51）。总生存率（两者P = 0.01）。结论：肿瘤病灶摄取⁶⁸ Ga-NODAGA-E[c(RGDyK)] ₂在所有级别的 NEN 患者中都很明显。高摄取与较差的预后相关。需要进一步的研究来确定⁶⁸ Ga-NODAGA-E[c(RGDyK)] ₂ PET/CT 是否可以成为识别适合接受针对整合素 α _v β _{3 治疗的患者的预测工具。}