Development of novel approach to diagnostic imaging of lung cancer with 18F-Nifene PET/CT using A/J mice treated with NNK.

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.