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

Abstract

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 18F-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 18F to obtain [18F]­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, [18F]­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.

Maternal embryonic leucine zipper kinase in cancer progress and therapeutic potentials

“…In addition to detecting MELK expression, other diagnostic tests may be used to determine the extent of cancer and its prognosis. Various imaging modalities, such as computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET) scans, are commonly used in this context [14].…”