Maternal embryonic leucine zipper kinase (MELK) plays an important role in the regulation of tumor cell growth. It is abundant in triple-negative breast cancers (TNBC), making it a promising target for molecular imaging and therapy. Based on the structure of a potent MELK inhibitor (OTSSP167) with high affinity, we developed a novel carbon-11 radiolabeled molecular probe ¹¹C-methoxy-OTSSP167, and evaluated its application in positron emission tomography (PET) imaging of TNBC. ¹¹C-methoxy-OTSSP167 was successfully synthesized and was identical to its non-radiolabeled compound methoxy-OTSSP167 in high-pressure liquid chromatography (HPLC) chromatogram. The obtained tracer had 10 ± 2% radiolabeling yield with a total synthesis time of 40 min. The radiochemical purity of the tracer was more than 95%. The maximum uptake (9.97 ± 0.70%) of ¹¹C-methoxy-OTSSP167 in MELK-overexpressing MDA-MB-231 cells was at 60 min in vitro. On PET, MDA-MB-231 tumors were clearly visible at 30, 60, and 90 min after injection of ¹¹C-methoxy-OTSSP167, while no obvious radioactivity accumulation was found in the low-MELK MCF-7 tumors. In vivo biodistribution data were consistent with the findings of the PET images. However, the radioactive tracer showed high uptake in normal organs such as liver and intestine, which may limit the application of the tracer. In addition, a markedly different MELK expression level in MDA-MBA-231 and MCF-7 tumors was verified via IHC staining. In conclusion, ¹¹C-methoxy-OTSSP167 was successfully developed and exhibited elevated uptake in MELK overexpressed tumor, indicating its potential for noninvasively imaging of MELK overexpressed TNBC.

母体胚胎亮氨酸拉链激酶 (MELK) 在调节肿瘤细胞生长中起重要作用。它在三阴性乳腺癌 (TNBC) 中含量丰富，使其成为分子成像和治疗的有希望的靶点。基于具有高亲和力的强效 MELK 抑制剂 (OTSSP167) 的结构，我们开发了一种新型碳 11 放射性标记分子探针¹¹ C-甲氧基-OTSSP167，并评估了其在 TNBC 正电子发射断层扫描 (PET) 成像中的应用。¹¹C-甲氧基-OTSSP167 合成成功，高压液相色谱 (HPLC) 色谱图与其未放射性标记的化合物甲氧基-OTSSP167 完全相同。获得的示踪剂具有 10 ± 2% 的放射性标记产率，总合成时间为 40 分钟。示踪剂的放射化学纯度大于95%。¹¹ C-甲氧基-OTSSP167 在过表达 MELK 的 MDA-MB-231 细胞中的最大吸收 (9.97 ± 0.70%)在体外60 分钟。在 PET 上，注射¹¹ C-甲氧基-OTSSP167后 30、60 和 90 分钟时，MDA-MB-231 肿瘤清晰可见，而在低 MELK MCF-7 肿瘤中未发现明显的放射性积累。体内生物分布数据与 PET 图像的结果一致。然而，放射性示踪剂在肝脏和肠道等正常器官中表现出高吸收，这可能限制了示踪剂的应用。此外，通过 IHC 染色证实了 MDA-MBA-231 和 MCF-7 肿瘤中显着不同的 MELK 表达水平。总之，¹¹ C-甲氧基-OTSSP167 已成功开发并在 MELK 过表达的肿瘤中表现出升高的摄取，表明其具有对 MELK 过表达的 TNBC 进行无创成像的潜力。