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

Abstract

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.

All-Cause Mortality Risk in Australian Women with Impaired Fasting Glucose and Diabetes

“…In addition, it has been predicted that diabetes is responsible for 4 million deaths worldwide in 2010 [ 15 ]. In Australia, diabetes is a growing disease with 280 new cases diagnosed every day [ 18 ].…”

Micro-CT acquisition and image processing to track and characterize pulmonary nodules in mice

“…Single photon emission computed tomography (SPECT) and positron emission tomography (PET) can be used to detect lung cancers and can provide molecular and metabolic activity of tumours [35][36][37][38] , but their limitations are poor spatial resolution (≤1 mm in SPECT 39 and >1 mm in PET) 40 , long scanning time and require the use of radioisotopes. Depending on the amount of radioactivity injected, the scanning time for SPECT imaging is 10 -50 min per animal [41][42][43] and PET imaging is 15 -60 min per animal [44][45][46][47] .To co-register detailed anatomical localisation with molecular information, commercial small animal SPECT (e.g., nanoScan SPECT/CT, Mediso), PET (e.g., nanoScan PET/CT, Mediso) and optical (e.g., IVIS SpectrumCT, PerkinElmer) imaging scanners are usually integrated x-ray CT inside the same imaging gantry or platform.…”