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 (V_d, 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.

zeste同源物2（EZH2）的增强子负责组蛋白H3（H3K27）赖氨酸27的甲基化，导致转录抑制。因此，EZH2与包括癌症在内的多种疾病有关，因为过表达的EZH2可以下调癌症抑制基因。因此，EZH2成为癌症治疗和诊断的有希望的靶标，EZH2的体内成像对于诊断和治疗监测至关重要。在本工作中，我们放射性标记了EZH2的特异性抑制剂[ ¹¹ C] EI1，研究了其药代动力学并进行了微型PET / CT成像。结果显示[ ¹¹ C] EI1在血液中的半衰期为3.4分钟。Micro PET / CT成像显示[ ¹¹C] EI1可以进入包括肝，胃和肠道在内的主要器官，并且可以被未标记的EI1阻断，从而导致明显的表观分布体积明显不同（V _d，阻断作用为2.8 mL，基线为17.4 ml），这验证了[ ¹¹ C] EI1对EZH2的特异性亲和力，并说明了EZH2在主要器官中的分布。结果表明，[ ¹¹ C] EI1可以作为EZH2 PET成像的示踪剂，用于EZH2相关疾病（尤其是癌症）的诊断和治疗监测。