Abstract
Enhancer of zeste homolog 2 (EZH2) is responsible for the methylation of lysine 27 of histone H3 (H3K27) leading to transcriptional repression. Consequently, EZH2 is related with several diseases including cancers, as overexpressed EZH2 can down-regulate cancer suppressor genes. Therefore, EZH2 became a promising target for cancer treatment and diagnosis and in vivo imaging of EZH2 is critical for diagnosis and treatment monitor. In the present work, we radiolabeled a specific inhibitor of EZH2, [11C]EI1, investigated its pharmacokinetics and performed micro PET/CT imaging. Results showed that the half-life of the [11C]EI1 in blood was 3.4 min. Micro PET/CT imaging showed that the [11C]EI1 can enter the major organs including liver, stomach, and intestine and can be blocked by the unlabeled EI1 resulting in a significant distinct between apparent distribution volumes (Vd, 2.8 mL for blocking versus 17.4 ml for baseline), which validated the specific affinity of the [11C]EI1 against EZH2 and illustrated the distribution of EZH2 in major organs. The results indicated that the [11C]EI1 can be a tracer for EZH2 PET imaging used in diagnosis and therapy monitor of EZH2 related diseases especially cancers.
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Acknowledgements
This work was supported by a pilot funding from the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital (CW) and Tianjin science and technology commission (17JCYBJC25800, 17YFZCSY00670). The author HW gratefully acknowledges financial support by China Scholarship Council (CSC). The authors are grateful to the Athinoula A. Martinos Center Radiopharmacy Lab staff for the assistant in radiochemistry.
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Wang, H., Lan, Y., Bai, P. et al. Radiosynthesis of [11C]EI1 for imaging EZH2 using positron emission tomography. Med Chem Res 29, 2106–2111 (2020). https://doi.org/10.1007/s00044-020-02633-1
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DOI: https://doi.org/10.1007/s00044-020-02633-1