Preclinical evaluation of [99mTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT
Preclinical evaluation of [99mTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT
复制标题
[99mTc]Tc标记的抗EpCAM纳米抗体用于EpCAM受体表达免疫SPECT/CT成像的临床前评估
DOI：
10.1007/s00259-021-05670-z
复制
发表时间：
2022-01-11
影响因子：
9.1
通讯作者：
Wang, Fan
中科院分区：
文献类型：
--
作者：
Liu, Tianyu;Wu, Yue;Wang, Fan
目的上皮细胞粘附分子（EpCAM）的过度表达在几乎所有上皮源性肿瘤的发生和发展中起重要作用。监测EpCAM在肿瘤中的表达可用于癌症患者的诊断、分期和预后，以及指导EpCAM靶向药物的个体化治疗。在这项研究中，我们描述了合成和评价的位点特异性[99 mTc] Tc标记的EpCAM靶向nanobody的SPECT/CT成像EpCAM expression.MethodsWe首先制备的[99 mTc]Tc-HYNIC-G4 K，然后，它是位点特异性连接到EpCAM靶向nanobody NB 4。[99 mTc] Tc-NB_4在HT-29细胞中的体外特性（EpCAM阳性）和HL-60（EpCAM阴性）细胞，体内研究采用小动物SPECT/CT在皮下肿瘤模型和淋巴结转移模型中验证[99 mTc] Tc-NB 4的特异性靶向能力和潜在的应用价值。NB 4在体外和体内均表现出高EpCAM特异性。SPECT/CT显像显示，[99 mTc] Tc-NB 4从血液和正常器官（肾脏除外）中迅速清除，与HL-60肿瘤相比，HT-29肿瘤清晰可见。HT-29肿瘤对[99 mTc] Tc-NB_4的摄取值从注射后0.5h的3.77 ± 0.39%ID/g增加到注射后12 h的5.53 ± 0.82%ID/g。结论[99 mTc] Tc-NB 4是一种广谱、特异、敏感的SPECT放射性示踪剂，可用于上皮性肿瘤EpCAM表达的无创显像，具有很大的临床应用潜力。
PurposeOverexpression 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 [99mTc]Tc-labeled EpCAM-targeted nanobody for the SPECT/CT imaging of EpCAM expression.MethodsWe first prepared the [99mTc]Tc-HYNIC-G4K; then, it was site-specifically connected to EpCAM-targeted nanobody NB4. The in vitro characteristics of [99mTc]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 [99mTc]Tc-NB4.Results[99mTc]Tc-NB4 displayed a high EpCAM specificity both in vitro and in vivo. SPECT/CT imaging revealed that [99mTc]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 [99mTc]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 [99mTc]Tc-NB4 SPECT/CT could clearly image tumor-draining lymph nodes.Conclusion[99mTc]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.