The diagnostic value of 68Ga-NOTA-MAL-Cys-MZHER2:342 PET/CT imaging for HER2-positive lung adenocarcinoma

Background: The human epidermal growth factor receptor 2 gene (HER2) has been identified as a potential therapeutic target in lung adenocarcinoma (LUAD). Non-invasive positron emission tomography (PET) imaging provides a reliable strategy for in vivo determination of HER2 expression through whole-body detection of abnormalities. The PET tracer Ga-68-NOTA-MAL-Cys-MZHER(2:342) has shown promising results for HER2-positive breast and gastric cancers. This study aims to evaluate the performance of Ga-68-NOTA-MAL-Cys-MZHER(2:342)in vitro and in vivo models and in clinical patients with HER2-positive LUAD. Methods: NOTA-MAL-Cys-MZHER(2:342) was synthesized and labeled with Ga-68. Cell uptake, cell binding ability, and stability studies of Ga-68-NOTA-MAL-Cys-MZHER(2:342) were assessed both in the Calu-3 lung cancer (LC) cell line and normal mice. In vivo assessment in tumor-bearing mice was conducted using microPET imaging and biodistribution experiments. Additionally, preliminary PET/CT imaging analysis was performed on HER2-positive LC patients. Results: Ga-68-NOTA-MAL-Cys-MZHER(2:342) was prepared with a radiochemical purity (RCP) exceeding 95%. The tracer demonstrated high cell uptake in HER2-overexpressing Calu-3 cells, with an IC50 of 158.9, an adequate 1.73 nM. Good stability was exhibited both in vitro and in vivo. MicroPET imaging of Calu-3-bearing mice revealed high tumor uptake and notable tumor-to-background ratios. Positive outcomes were also observed in two HER2-positive LUAD patients. Conclusion: Ga-68-NOTA-MAL-Cys-MZHER(2:342) demonstrated satisfactory stability, sensitivity, and specificity. These findings suggest that Ga-68-NOTA-MAL-Cys-MZHER(2:342) PET/CT imaging provides a novel tool for non-invasive visual assessment of HER2 expression in LUAD patients.