肺大细胞神经内分泌癌（LCNEC）是恶性程度高、预后差的罕见癌症，早期诊断准确率低是影响其预后的主要因素。靶向特异性分子的PET分子影像可推动恶性肿瘤的诊断和治疗。前期，我们研究发现肺LCNEC细胞系特异性高表达II型囊泡单胺转运体(VMAT2)，且对VMAT2的示踪药物18F-AV133具有特异性高摄取，而抑制VMAT2降低了肺LCNEC细胞的增殖和迁移能力，提示VMAT2可能在肺LCNEC的发生发展中有重要作用，是其PET显像的潜在靶点。在本项目中，我们将进一步在细胞模型和裸鼠肿瘤模型中，运用分子生物学和细胞生物学技术，揭示VMAT2在肺LCNEC中的作用及分子机制，从而验证其作为肺LCNEC显像靶点的可行性；并用放射自显影和microPET显像等技术手段评价18F-AV133 PET显像在肺LCNEC影像学研究中的应用潜力，以期为肺LCNEC的临床PET显像或干预研究提供新的思路。

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer with high malignancy and poor prognosis. The low accuracy of early diagnosis is the main factor affecting the prognosis. Molecular imaging with PET targeting to specific tumor marker could greatly promote the diagnosis and treatment of malignant tumors. Previously, we found that vesicular monoamine transporter 2 (VMAT2) was specifically highly-expressed in pulmonary LCNEC cells among several different lung cancer cells. A high and specific uptake of 18F-FP-(+)-DTBZ (18F-AV133), a reported 18F labeled VMAT2 ligand, was also observed in the lung LCNEC cell line. Furthermore, inhibition of VMAT2 suppressed the proliferation and migration ability of pulmonary LENEC cells. These results suggested that VMAT2 may play a role in the progression of pulmonary LENEC, and VMAT2 is likely a potential target for pulmonary LCNEC molecular imaging. In this study, we will further comprehensively reveal the underlying mechanism and validate the scientific feasibility of VMAT2 as an imaging target for the pulmonary LCNEC in series of lung cancer cell lines and athymic nude mouse tumor model with the techniques of both molecular biology and cell biology. Then we will systematically evaluate the potential of 18F-AV133 for pulmonary LCNEC imaging using autoradiography, microPET imaging and other nuclear medicine technologies. Our objective is aimed at revealing the role of VMAT2 and exploring the application potential of its 18F labeled ligand in pulmonary LCNEC. We hope our research could provide a new perspective for clinical PET imaging and treatment of pulmonary LCNEC.