A high level of EpCAM overexpression in lung cancer makes this protein a promising target for targeted therapy. Radionuclide visualization of EpCAM expression would facilitate the selection of patients potentially benefiting from such treatment. Single-photon computed tomography (SPECT) using99mTc-labeled engineered scaffold protein DARPin Ec1 has shown its effectiveness in imaging tumors with overexpression of EpCAM in preclinical studies, providing high contrast just a few hours after injection. This first-in-human study aimed to evaluate the safety and distribution of [99mTc]Tc(CO)3-(HE)3-Ec1 in patients with primary lung cancer. Twelve lung cancer patients were injected with 300.7 ± 103.2 MBq of [99mTc]Tc(CO)3-(HE)3-Ec1. Whole-body planar imaging (at 2, 4, 6 and 24 h after injection) and SPECT/CT of the lung (at 2, 4, and 6 h) were performed. The patients’ vital signs and possible side effects were monitored up to 7 days after injection. The patients tolerated the injection of [99mTc]Tc(CO)3-(HE)3-Ec1 well, and their somatic condition remained normal during the entire follow-up period. There were no abnormalities in blood and urine tests after injection of [99mTc]Tc(CO)3-(HE)3-Ec1. The highest absorbed doses were in the kidneys, liver, pancreas, thyroid, gallbladder wall, and adrenals. There was also a relatively high accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the small and large intestines, pancreas and thyroid. According to the SPECT/CT, accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 in the lung tumor was found in all patients included in the study. Intensive accumulation of [99mTc]Tc(CO)3-(HE)3-Ec1 was also noted in regional metastases. [99mTc]Tc(CO)3-(HE)3-Ec1 can potentially be considered a diagnostic tracer for imaging EpCAM expression in lung cancer patients and other tumors with overexpression of EpCAM.
肺癌中上皮细胞黏附分子（EpCAM）的高水平过表达使其成为靶向治疗的一个有前景的靶点。EpCAM表达的放射性核素可视化将有助于筛选可能从此类治疗中获益的患者。临床前研究显示，使用99mTc标记的工程支架蛋白DARPin Ec1进行单光子发射计算机断层扫描（SPECT）可有效成像EpCAM过表达的肿瘤，并在注射后数小时内即提供高对比度图像。这项首次人体研究旨在评估[99mTc]Tc(CO)3-(HE)3-Ec1在原发性肺癌患者中的安全性和分布情况。12名肺癌患者注射了300.7 ± 103.2 MBq的[99mTc]Tc(CO)3-(HE)3-Ec1。进行了全身平面成像（注射后2、4、6和24小时）和肺部SPECT/CT扫描（注射后2、4和6小时）。在注射后7天内监测患者的生命体征和可能的副作用。患者对[99mTc]Tc(CO)3-(HE)3-Ec1注射耐受良好，在整个随访期间身体状况保持正常。注射[99mTc]Tc(CO)3-(HE)3-Ec1后，血液和尿液检查未见异常。吸收剂量最高的器官为肾脏、肝脏、胰腺、甲状腺、胆囊壁和肾上腺。[99mTc]Tc(CO)3-(HE)3-Ec1在小肠、大肠、胰腺和甲状腺也有相对较高的蓄积。根据SPECT/CT结果，所有纳入研究的患者均发现肺肿瘤中有[99mTc]Tc(CO)3-(HE)3-Ec1的蓄积。在区域转移灶中也观察到[99mTc]Tc(CO)3-(HE)3-Ec1的明显蓄积。[99mTc]Tc(CO)3-(HE)3-Ec1有望成为诊断肺癌患者及其他EpCAM过表达肿瘤中EpCAM表达的示踪剂。
肿瘤(癌症)患者之家