Tianyu Liu1, Yue Wu1, Linqing Shi1, Liqiang Li1, Biao Hu1, Yanpu Wang1, Hannan Gao1, Xiaolu Yu2, Xin Zhang1, Huiyun Zhao1, Yakun Wan3, Bing Jia4,5, Fan Wang6,7. 1. Medical Isotopes Research Center, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, People's Republic of China. 2. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, People's Republic of China. 3. Shanghai Novamab Biopharmaceuticals Co., Ltd, Shanghai, People's Republic of China. 4. Medical Isotopes Research Center, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, People's Republic of China. jiabing@bjmu.edu.cn. 5. Department of Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, People's Republic of China. jiabing@bjmu.edu.cn. 6. Medical Isotopes Research Center, Department of Radiation Medicine, School of Basic Medical Sciences, Peking University, Beijing, 100191, People's Republic of China. wangfan@bjmu.edu.cn. 7. Key Laboratory of Protein and Peptide Pharmaceuticals, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, People's Republic of China. wangfan@bjmu.edu.cn.
Abstract
PURPOSE: 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 [99mTc]Tc-labeled EpCAM-targeted nanobody for the SPECT/CT imaging of EpCAM expression. METHODS: We 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.
PURPOSE: 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 [99mTc]Tc-labeled EpCAM-targeted nanobody for the SPECT/CT imaging of EpCAM expression. METHODS: We 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.
Authors: G Riethmüller; E Holz; G Schlimok; W Schmiegel; R Raab; K Höffken; R Gruber; I Funke; H Pichlmaier; H Hirche; P Buggisch; J Witte; R Pichlmayr Journal: J Clin Oncol Date: 1998-05 Impact factor: 44.544
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Authors: S V Litvinov; M Balzar; M J Winter; H A Bakker; I H Briaire-de Bruijn; F Prins; G J Fleuren; S O Warnaar Journal: J Cell Biol Date: 1997-12-01 Impact factor: 10.539
Authors: P Went; M Vasei; L Bubendorf; L Terracciano; L Tornillo; U Riede; J Kononen; R Simon; G Sauter; P A Baeuerle Journal: Br J Cancer Date: 2006-01-16 Impact factor: 7.640