BACKGROUND 68Ga-EMP-100 is a novel positron emission tomography (PET) ligand that directly targets tumoral c-MET expression. Upregulation of the receptor tyrosin kinase c-MET in renal cell carcinoma (RCC) is correlated with overall survival in metastatic disease (mRCC). Clinicopathological staging of c-MET expression could improve patient management prior to systemic therapy with for instance inhibitors targeting c-MET such as cabozantinib. We present the first in-human data of 68Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC. METHODS Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent 68Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUVmean) and SUVmax measurements. Additionally, metastatic sites on PET were compared to contrast-enhanced computed tomography (CT) and the respective, quantitative PET parameters were assessed and then compared inter- and intra-individually. RESULTS Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUVmax of 4.35 and SUVmean of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUVmax 9.05 (4.86-29.16)), followed by bone metastases (SUVmax 5.56 (0.97-15.85)), and lymph node metastases (SUVmax 3.90 (2.13-6.28)) and visceral metastases (SUVmax 3.82 (0.11-16.18)). The occurrence of visually PET-negative lesions (20.7%) was distributed heterogeneously on an intra- and inter-individual level; the largest proportion of PET-negative metastatic lesions were lung and liver metastases. The highest physiological 68Ga-EMP-100 accumulation besides the urinary bladder content was seen in the kidneys, followed by moderate uptake in the liver and the spleen, whereas significantly lower uptake intensity was observed in the pancreas and the intestines. CONCLUSION Targeting c-MET expression, 68Ga-EMP-100 shows distinctly elevated uptake in mRCC patients with partially high inter- and intra-individual differences comprising both c-MET-positive and c-MET-negative lesions. Our first clinical results warrant further systemic studies investigating the clinical use of 68Ga-EMP-100 as a biomarker in mRCC patients.

中文翻译：

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68Ga-EMP-100 PET/CT-一种用于可视化转移性肾细胞癌中 c-MET 表达的新型配体-首次人体生物分布和成像结果。

背景 68Ga-EMP-100 是一种直接靶向肿瘤 c-MET 表达的新型正电子发射断层扫描 (PET) 配体。肾细胞癌 (RCC) 中受体酪氨酸激酶 c-MET 的上调与转移性疾病 (mRCC) 的总生存期相关。c-MET 表达的临床病理学分期可以改善在全身治疗之前的患者管理，例如针对 c-MET 的抑制剂，如卡博替尼。我们提供了 mRCC 患者中 68Ga-EMP-100 的首个人体数据，用于评估转移灶和原发性 RCC 的摄取特征。方法 12 名 mRCC 患者在预期的卡博替尼治疗前接受了 68Ga-EMP-100 PET/CT 成像。我们通过标准摄取值 (SUVmean) 和 SUVmax 测量值比较了 mRCC 病变在正常器官中的生物分布和肿瘤摄取。此外，将 PET 上的转移部位与对比增强计算机断层扫描 (CT) 进行比较，并评估各自的定量 PET 参数，然后在个体内和个体内进行比较。结果 总体而言，分析了 87 个肿瘤病灶。其中，68/87 (79.3%) 被视觉评定为 c-MET 阳性，包括 4.35 的中值 SUVmax 和 2.52 的 SUVmean。比较不同的肿瘤部位，发现原发部位肿瘤负荷的摄取强度最高（SUVmax 9.05（4.86-29.16）），其次是骨转移（SUVmax 5.56（0.97-15.85））和淋巴结转移（SUVmax 3.90（ 2.13-6.28)) 和内脏转移 (SUVmax 3.82 (0.11-16.18))。视觉 PET 阴性病变的发生率（20.7%）在个体内部和个体之间分布不均；PET阴性转移灶的最大比例是肺和肝转移。除膀胱内容物外，肾脏中最高的生理 68Ga-EMP-100 积累，其次是肝脏和脾脏中度摄取，而在胰腺和肠道中观察到显着较低的摄取强度。结论 针对 c-MET 表达，68Ga-EMP-100 在 mRCC 患者中显示出明显升高的摄取，具有部分高的个体间和内部差异，包括 c-MET 阳性和 c-MET 阴性病变。我们的第一个临床结果需要进一步的系统研究，调查 68Ga-EMP-100 作为 mRCC 患者的生物标志物的临床应用。其次是在肝脏和脾脏中度摄取，而在胰腺和肠道中观察到显着较低的摄取强度。结论 针对 c-MET 表达，68Ga-EMP-100 在 mRCC 患者中显示出明显升高的摄取，具有部分高的个体间和内部差异，包括 c-MET 阳性和 c-MET 阴性病变。我们的第一个临床结果需要进一步的系统研究，调查 68Ga-EMP-100 作为 mRCC 患者的生物标志物的临床应用。其次是在肝脏和脾脏中度摄取，而在胰腺和肠道中观察到显着较低的摄取强度。结论 针对 c-MET 表达，68Ga-EMP-100 在 mRCC 患者中显示出明显升高的摄取，具有部分高的个体间和内部差异，包括 c-MET 阳性和 c-MET 阴性病变。我们的第一个临床结果需要进一步的系统研究，调查 68Ga-EMP-100 作为 mRCC 患者的生物标志物的临床应用。68Ga-EMP-100 在 mRCC 患者中显示出明显升高的摄取，具有部分高的个体间和内部差异，包括 c-MET 阳性和 c-MET 阴性病变。我们的第一个临床结果需要进一步的系统研究，调查 68Ga-EMP-100 作为 mRCC 患者的生物标志物的临床应用。68Ga-EMP-100 在 mRCC 患者中显示出明显升高的摄取，具有部分高的个体间和内部差异，包括 c-MET 阳性和 c-MET 阴性病变。我们的第一个临床结果需要进一步的系统研究，调查 68Ga-EMP-100 作为 mRCC 患者的生物标志物的临床应用。