Development of novel approach to diagnostic imaging of lung cancer with (18)F-Nifene PET/CT using A/J mice treated with NNK.
Development of novel approach to diagnostic imaging of lung cancer with (18)F-Nifene PET/CT using A/J mice treated with NNK.
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DOI：
10.14312/2052-4994.2013-20
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发表时间：
2013-06
期刊：
影响因子：
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通讯作者：
Grando SA
中科院分区：
文献类型：
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作者：
Galitovskiy V;Kuruvilla SA;Sevriokov E;Corches A;Pan ML;Kalantari-Dehaghi M;Chernyavsky AI;Mukherjee J;Grando SA
发展肺癌早期诊断的新方法是当代临床和实验肿瘤学的主要任务之一。本研究利用烟草亚硝胺4-（甲基亚硝胺）-1-（3-吡啶基）-1-丁酮（NNK）诱导A/J小鼠肺癌作为动物模型，开发一种新的肺癌早期诊断成像技术。A/J小鼠肺癌细胞过表达烟碱乙酰胆碱受体。在NNK治疗后8个月进行纵向CT扫描，随后用18F-Nifene进行PET/CT扫描，该18F-Nifene与α4制造的烟碱受体具有高亲和力。肺的PET/CT扫描也得到了离体。CT显示8个月大的nnk治疗小鼠出现肺结节，而对照组小鼠未见肿瘤。活体动物尸检前的成像允许通过PET/CT和组织病理学结果的肿瘤负荷结果的相关性。nnk处理小鼠的肺中可见到大量的18f -尼芬，而对照组小鼠的肺仅显示少量的18f -尼芬摄取。在体内和离体肺组织中对18F-Nifene结合程度和量的定量分析表明，选择性标记表达丰富α4烟碱受体亚基的肿瘤结节具有较高的肿瘤/非肿瘤比例。为了比较，我们使用用于肺癌影像学诊断的18F-FDG进行PET/CT研究。18F-FDG的肿瘤/非肿瘤比率低于18F-Nifene。因此，我们开发了一种使用18F-Nifene PET/CT进行肺癌早期诊断的新型诊断成像方法。该技术允许对活体小鼠肺肿瘤进行定量评估，这对于确定肿瘤的大小和位置至关重要，并且具有显著的临床意义。
Development of novel methods of early diagnosis of lung cancer is one of the major tasks of contemporary clinical and experimental oncology. In this study, we utilized the tobacco nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung cancer in A/J mice as an animal model for development of a new imaging technique for early diagnosis of lung cancer. Lung cancer cells in A/J mice overexpress nicotinic acetylcholine receptors. Longitudinal CT scans were carried out over a period of 8 months after NNK treatment, followed by PET/CT scans with 18F-Nifene that binds to α4-made nicotinic receptors with high affinity. PET/CT scans of lungs were also obtained ex vivo. CT revealed the presence of lung nodules in 8-month NNK-treated mice, while control mice had no tumors. Imaging of live animals prior to necropsy allowed correlation of results of tumor load via PET/CT and histopathological findings. Significant amount of 18F-Nifene was seen in the lungs of NNK-treated mice, whereas lungs of control mice showed only minor uptake of 18F-Nifene. Quantitative analysis of the extent and amount of 18F-Nifene binding in lung in vivo and ex vivo demonstrated a higher tumor/nontumor ratio due to selective labeling of tumor nodules expressing abundant α4 nicotinic receptor subunits. For comparison, we performed PET/CT studies with 18F-FDG, which is used for the imaging diagnosis of lung cancer. The tumor/nontumor ratios for 18F-FDG were lower than for 18F-Nifene. Thus, we have developed a novel diagnostic imaging approach to early diagnosis of lung cancer using 18F-Nifene PET/CT. This technique allows quantitative assessment of lung tumors in live mice, which is critical for establishing tumor size and location, and also has salient clinical implications.