¹¹C-ethoxy-OTSSP167 inhibits maternal embryo leucine zipper kinase for PET / CT imaging of triple-negative breast cancer

Objectives: Breast cancer seriously endangers the health of middle-aged and elderly women. At present, the diagnosis and treatment of Non-triple-negative breast cancer patients are maturing, but there is no effective diagnosis and treatment for patients with triple negative breast cancer (TNBC). A large number of literatures confirm that MELK (maternal embryo leucine zipper kinase) is highly expressed in TNBC. Based on this, OTSSP167 (a small molecule compound MELK) was significantly inhibited, and a new diagnostic TNBC targeted imaging 11C-ethoxy-OTSSP167, which is a small molecule, is easy to prepare and can be used to dynamically monitor the changes of TNBC patients in real time.

Methods: Breast cancer cell line, MDA-MB-231-UR and MCF-7, were sued as MELK overexpression and underexpression models, respectively. OTSSP167 was labeled with ¹¹C using Ethylene glycol bis-p-toluenesulfonate and N, N-diisopropylethylamine (ethoxy). MicroPET/CT imaging, biodistribution, and autoradiography studies were performed at the time of 30min, 60min, 90min and 120min in mice bearing MDA-MB-231-UR tumors after injection of ¹¹C-ethoxy-OTSSP167 to verify the targeting ability of the tracer.

Results: ¹¹C-ethoxy-OTSSP167 was successfully synthesized with labeling efficiency. MicroPET/CT images, biodistribution, and autoradiography studies showed high uptake of the tracer in MDA-MB-231-UR tumors. OTSSP167 caused dose- and time-dependent growth inhibition and apoptosis in melanoma cells in vitro, and suppressed MDA-MB-231-UR tumor growth in vivo. Conclusions: OTSSP167, an MELK inhibitor, inhibits tumor growth and MELK expression. ¹¹C-ethoxy-OTSSP167, an easily-prepared probe, can be used to visualize MELK positive tumors and to monitor the effect of OTSSP167 therapy, suggesting its prospective clinical application.