Radiosynthesis of [11C]EI1 for imaging EZH2 using positron emission tomography

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.