AUTHOR=Li Shu , Wang Ke , Zhu Xue , Pan Donghui , Wang Ling , Guo Xu , Gao Xiaomin , Luo Qing , Wang Xun 

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

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1447500

DOI=10.3389/fmed.2024.1447500

ISSN=2296-858X

ABSTRACT=<sec id="sec1"><title>Background</title><p>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 <italic>in vivo</italic> determination of HER2 expression through whole-body detection of abnormalities. The PET tracer <sup>68</sup>Ga-NOTA-MAL-Cys-MZHER<sub>2:342</sub> has shown promising results for HER2-positive breast and gastric cancers. This study aims to evaluate the performance of <sup>68</sup>Ga-NOTA-MAL-Cys-MZHER<sub>2:342</sub><italic>in vitro</italic> and <italic>in vivo</italic> models and in clinical patients with HER2-positive LUAD.</p></sec><sec id="sec2"><title>Methods</title><p>NOTA-MAL-Cys-MZHER<sub>2:342</sub> was synthesized and labeled with <sup>68</sup>Ga. Cell uptake, cell binding ability, and stability studies of <sup>68</sup>Ga-NOTA-MAL-Cys-MZHER<sub>2:342</sub> were assessed both in the Calu-3 lung cancer (LC) cell line and normal mice. <italic>In vivo</italic> 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.</p></sec><sec id="sec3"><title>Results</title><p><sup>68</sup>Ga-NOTA-MAL-Cys-MZHER<sub>2:342</sub> was prepared with a radiochemical purity (RCP) exceeding 95%. The tracer demonstrated high cell uptake in HER2-overexpressing Calu-3 cells, with an IC<sub>50</sub> of 158.9, an adequate 1.73 nM. Good stability was exhibited both <italic>in vitro</italic> and <italic>in vivo</italic>. 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.</p></sec><sec id="sec4"><title>Conclusion</title><p><sup>68</sup>Ga-NOTA-MAL-Cys-MZHER<sub>2:342</sub> demonstrated satisfactory stability, sensitivity, and specificity. These findings suggest that <sup>68</sup>Ga-NOTA-MAL-Cys-MZHER<sub>2:342</sub> PET/CT imaging provides a novel tool for non-invasive visual assessment of HER2 expression in LUAD patients.</p></sec>