Galitovskiy V, Kuruvilla S A, Sevriokov E, Corches A, Pan M L, Kalantari-Dehaghi M, Chernyavsky A I, Mukherjee J, Grando S A
Department of Dermatology, University of California-Irvine, Irvine, CA 92697, USA.
Preclinical Imaging, Department of Radiological Sciences, University of California-Irvine, Irvine, CA 92697, USA.
J Cancer Res Ther (Manch). 2013 Jun;1(4):128-137. doi: 10.14312/2052-4994.2013-20. Epub 2013 May 29.
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 F-Nifene that binds to 4-made nicotinic receptors with high affinity. PET/CT scans of lungs were also obtained 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 PET/CT and histopathological findings. Significant amount of F-Nifene was seen in the lungs of NNK-treated mice, whereas lungs of control mice showed only minor uptake of F-Nifene. Quantitative analysis of the extent and amount of F-Nifene binding in lung and demonstrated a higher tumor/nontumor ratio due to selective labeling of tumor nodules expressing abundant 4 nicotinic receptor subunits. For comparison, we performed PET/CT studies with F-FDG, which is used for the imaging diagnosis of lung cancer. The tumor/nontumor ratios for F-FDG were lower than for F-Nifene. Thus, we have developed a novel diagnostic imaging approach to early diagnosis of lung cancer using F-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.
开发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。在本研究中，我们利用烟草亚硝胺4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮（NNK）诱导A/J小鼠患肺癌，作为开发肺癌早期诊断新成像技术的动物模型。A/J小鼠中的肺癌细胞过表达烟碱型乙酰胆碱受体。在NNK治疗后的8个月内进行纵向CT扫描，随后用与4型烟碱受体具有高亲和力的F-Nifene进行PET/CT扫描。还对肺部进行了PET/CT扫描。CT显示，在接受NNK治疗8个月的小鼠中存在肺结节，而对照小鼠没有肿瘤。在尸检前对活体动物进行成像，可将肿瘤负荷的PET/CT结果与组织病理学发现相关联。在接受NNK治疗的小鼠肺部可见大量F-Nifene，而对照小鼠的肺部仅显示少量F-Nifene摄取。对肺部F-Nifene结合的程度和量进行定量分析，结果表明，由于表达丰富的4型烟碱受体亚基的肿瘤结节被选择性标记，肿瘤/非肿瘤比值更高。为作比较，我们用用于肺癌成像诊断的F-FDG进行了PET/CT研究。F-FDG的肿瘤/非肿瘤比值低于F-Nifene。因此，我们开发了一种使用F-Nifene PET/CT进行肺癌早期诊断的新型诊断成像方法。该技术可对活体小鼠的肺部肿瘤进行定量评估，这对于确定肿瘤大小和位置至关重要，并且还具有重要的临床意义。
