Liu Tianyu, Wu Yue, Shi Linqing, Li Liqiang, Hu Biao, Wang Yanpu, Gao Hannan, Yu Xiaolu, Zhang Xin, Zhao Huiyun, Wan Yakun, Jia Bing, Wang Fan
Medical Isotopes Research Center, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, People's Republic of China.
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China.
Eur J Nucl Med Mol Imaging. 2022 May;49(6):1810-1821. doi: 10.1007/s00259-021-05670-z. Epub 2022 Jan 11.
Overexpression of epithelial cell adhesion molecule (EpCAM) plays essential roles in tumorigenesis and tumor progression in almost all epithelium-derived cancer. Monitoring EpCAM expression in tumors can be used for the diagnosis, staging, and prognosis of cancer patients, as well as guiding the individualized treatment of EpCAM-targeted drugs. In this study, we described the synthesis and evaluation of a site-specifically [Tc]Tc-labeled EpCAM-targeted nanobody for the SPECT/CT imaging of EpCAM expression.
We first prepared the [Tc]Tc-HYNIC-GK; then, it was site-specifically connected to EpCAM-targeted nanobody NB4. The in vitro characteristics of [Tc]Tc-NB4 were investigated in HT-29 (EpCAM positive) and HL-60 (EpCAM negative) cells, while the in vivo studies were performed using small-animal SPECT/CT in the subcutaneous tumor models and the lymph node metastasis model to verify the specific targeting capacity as well as the potential applications of [Tc]Tc-NB4.
[Tc]Tc-NB4 displayed a high EpCAM specificity both in vitro and in vivo. SPECT/CT imaging revealed that [Tc]Tc-NB4 was cleared rapidly from the blood and normal organs except for the kidneys, and HT-29 tumors were clearly visualized in contrast with HL-60 tumors. The uptake value of [Tc]Tc-NB4 in HT-29 tumors was increased continuously from 3.77 ± 0.39%ID/g at 0.5 h to 5.53 ± 0.82%ID/g at 12 h after injection. Moreover, the [Tc]Tc-NB4 SPECT/CT could clearly image tumor-draining lymph nodes.
[Tc]Tc-NB4 is a broad-spectrum, specific, and sensitive SPECT radiotracer for the noninvasive imaging of EpCAM expression in the epithelium-derived cancer and revealed a great potential for the clinical translation.
上皮细胞黏附分子（EpCAM）的过表达在几乎所有上皮来源的癌症的肿瘤发生和肿瘤进展中起着至关重要的作用。监测肿瘤中EpCAM的表达可用于癌症患者的诊断、分期和预后评估，以及指导EpCAM靶向药物的个体化治疗。在本研究中，我们描述了一种用于EpCAM表达的SPECT/CT成像的位点特异性[锝（Tc）]Tc标记的EpCAM靶向纳米抗体的合成与评估。
我们首先制备了[Tc]Tc-HYNIC-GK；然后，将其位点特异性连接到EpCAM靶向纳米抗体NB4上。在HT-29（EpCAM阳性）和HL-60（EpCAM阴性）细胞中研究了[Tc]Tc-NB4的体外特性，同时在皮下肿瘤模型和淋巴结转移模型中使用小动物SPECT/CT进行体内研究，以验证[Tc]Tc-NB4的特异性靶向能力及其潜在应用。
[Tc]Tc-NB4在体外和体内均表现出高EpCAM特异性。SPECT/CT成像显示，[Tc]Tc-NB4除肾脏外迅速从血液和正常器官中清除，与HL-60肿瘤相比，HT-29肿瘤清晰可见。注射后0.5小时，[Tc]Tc-NB4在HT-29肿瘤中的摄取值从3.77±0.39%ID/g持续增加到12小时时的5.53±0.82%ID/g。此外，[Tc]Tc-NB4 SPECT/CT能够清晰地对引流肿瘤的淋巴结进行成像。
[Tc]Tc-NB4是一种用于上皮来源癌症中EpCAM表达无创成像的广谱、特异性和灵敏的SPECT放射性示踪剂，显示出巨大的临床转化潜力。
