[18F]F-ET-OTSSP167 Targets Maternal Embryo Leucine Zipper Kinase for PET Imaging of Triple-Negative Breast Cancer

Maternal embryo leucine zipper kinase (MELK) is a serine/ threonine kinase and is highly expressed in triple-negative breast cancer (TNBC). This study aimed to develop a F-18-radiolabeled tracer based on the structure of a small-molecule MELK inhibitor OTSSP167 and evaluate its application for PET imaging of MELK expression in TNBC. OTSSP167 was modified with ethylene glycol to adjust its pharmacokinetics and was then radiolabeled with F-18 to obtain [F-18]F-ET-OTSSP167 at a labeling yield of 7.14 +/- 2.19% and a molar activity of 16.23 +/- 1.13 MBq/nmol. In vitro binding assays showed differentiated binding affinities of [18F]F-ET-OTSSP167 in different breast cancer cell lines, with high uptake in MDA-MB-231 (mild MELK expression) and low uptake in MCF-7 (negative MELK expression). PET imaging revealed that MDA-MB-231 tumors could be clearly delineated in vivo, while low tracer uptake was observed in MCF-7 tumors. These findings were confirmed by ex vivo biodistribution studies and were consistent with the immunohistochemistry and tissue staining results. Tracer accumulation in MDA-MB-231 tumors was significantly inhibited by excess amounts of OTSSP167, indicating high specificity of the tracer. In summary, [F-18]F-ET-OTSSP167, an easily-prepared probe, can be used to visualize MELK positive tumors, demonstrating its promising clinical potential in selecting patients for MELK inhibitor therapy.

Automated summary

The study developed a F-18-radiolabeled tracer based on a small-molecule MELK inhibitor and evaluated its potential for PET imaging of MELK expression in TNBC. The tracer showed high uptake in MDA-MB-231 tumors, low uptake in MCF-7 tumors, and high specificity. These findings suggest promising clinical potential for selecting patients for MELK inhibitor therapy.