Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.
Department of Urology, University Hospital, LMU Munich, Munich, Germany.
Eur J Nucl Med Mol Imaging. 2022 Apr;49(5):1711-1720. doi: 10.1007/s00259-021-05596-6. Epub 2021 Oct 28.
Ga-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 Ga-EMP-100 in mRCC patients evaluating uptake characteristics in metastases and primary RCC.
Twelve patients with mRCC prior to anticipated cabozantinib therapy underwent Ga-EMP-100 PET/CT imaging. We compared the biodistribution in normal organs and tumor uptake of mRCC lesions by standard uptake value (SUV) and SUV 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.
Overall, 87 tumor lesions were analyzed. Of these, 68/87 (79.3%) were visually rated c-MET-positive comprising a median SUV of 4.35 and SUV of 2.52. Comparing different tumor sites, the highest uptake intensity was found in tumor burden at the primary site (SUV 9.05 (4.86-29.16)), followed by bone metastases (SUV 5.56 (0.97-15.85)), and lymph node metastases (SUV 3.90 (2.13-6.28)) and visceral metastases (SUV 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 Ga-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.
Targeting c-MET expression, Ga-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 Ga-EMP-100 as a biomarker in mRCC patients.
Ga-EMP-100 是一种新型正电子发射断层扫描（PET）配体，可直接靶向肿瘤 c-MET 表达。受体酪氨酸激酶 c-MET 在肾细胞癌（RCC）中的上调与转移性疾病（mRCC）的总生存率相关。在接受例如卡博替尼等靶向 c-MET 的抑制剂进行全身治疗之前，对 c-MET 表达进行临床病理分期可以改善患者管理。我们报告了 Ga-EMP-100 在 mRCC 患者中的首次人体数据，评估了转移灶和原发性 RCC 中摄取特征。
12 名接受预期卡博替尼治疗的 mRCC 患者接受了 Ga-EMP-100 PET/CT 成像。我们通过标准摄取值（SUV）和 SUV 测量比较了正常器官和肿瘤摄取的生物分布，并比较了 PET 上的转移部位与对比增强计算机断层扫描（CT），评估了各自的定量 PET 参数，并在个体间和个体内进行了比较。
总共分析了 87 个肿瘤病变。其中，68/87（79.3%）为视觉评定 c-MET 阳性，中位数 SUV 为 4.35，SUV 为 2.52。比较不同的肿瘤部位，原发部位肿瘤负荷的摄取强度最高（SUV9.05（4.86-29.16）），其次是骨转移（SUV5.56（0.97-15.85）），淋巴结转移（SUV3.90（2.13-6.28））和内脏转移（SUV3.82（0.11-16.18））。视觉上 PET 阴性病变（20.7%）的发生率在个体内和个体间呈异质性分布；最大比例的 PET 阴性转移性病变是肺和肝转移。除了膀胱内容物外，Ga-EMP-100 最高的生理摄取部位是肾脏，其次是肝脏和脾脏的中等摄取，而胰腺和肠道的摄取强度明显较低。
靶向 c-MET 表达，Ga-EMP-100 在 mRCC 患者中表现出明显升高的摄取，部分患者个体内和个体间差异较大，包括 c-MET 阳性和 c-MET 阴性病变。我们的初步临床结果证实了进一步的系统研究，以调查 Ga-EMP-100 作为 mRCC 患者生物标志物的临床应用。
