Abstract
1028
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. A new diagnostic TNBC targeted imaging 18F-PEG2-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 used as MELK overexpression and underexpression models, respectively. OTSSP167 was labeled with 18F using polyethylene glycol (PEG2). MicroPET imaging, biodistribution and autoradiography studies were performed at the time of 0.5h, 1h, 2h and 4h in mice bearing MDA-MB-231-UR and MCF-7 tumors after injection of 18F-PEG2-OTSSP167 to verify the targeting ability of the tracer.
Results: The labeling rate of 18F-PEG2-OTSSP167 was 91.00±2.04% (n=5), and the radiochemical purity after purification was 95.80±1.75% (n=5). Micro PET 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. 18F-PEG2-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.