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Preclinical evaluation of [99mTc]Tc-labeled anti-EpCAM nanobody for EpCAM receptor expression imaging by immuno-SPECT/CT
- Source :
- European Journal of Nuclear Medicine and Molecular Imaging. 49:1810-1821
- Publication Year :
- 2022
- Publisher :
- Springer Science and Business Media LLC, 2022.
-
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-infiltrating 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.
Details
- ISSN :
- 16197089 and 16197070
- Volume :
- 49
- Database :
- OpenAIRE
- Journal :
- European Journal of Nuclear Medicine and Molecular Imaging
- Accession number :
- edsair.doi.dedup.....c7a8eb9b9eca2fbf3dd8fd808ee00bc4