Chin Ng

Ferret Thoracic Anatomy by 2-Deoxy-2-(18F)Fluoro-D-Glucose (18F-FDG) Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) Imaging

Abstract The domestic ferret (Mustela putorius furo) has been a long-standing animal model used in the evaluation and treatment of human diseases. Molecular imaging techniques such as 2-deoxy-2-(18F)fluoro-D-glucose (18F-FDG) positron emission tomography (PET) would be an invaluable method of tracking disease in vivo, but this technique has not been reported in the literature. Thus, the aim of this study was to establish baseline imaging characteristics of PET/computed tomography (CT) with 18F-FDG in the ferret model. Twelve healthy female ferrets were anesthetized and underwent combined PET/CT scanning. After the images were fused, volumes of interest (VOIs) were generated in the liver, heart, thymus, and bilateral lung fields. For each VOI, standardized uptake values (SUVs) were calculated. Additional comparisons were made between radiotracer uptake periods (60, 90, and >90 minutes), intravenous and intraperitoneal injections of 18F-FDG, and respiratory gated and ungated acquisitions. Pulmonary structures and the surrounding thoracic and upper abdominal anatomy were readily identified on the CT scans of all ferrets and were successfully fused with PET. VOIs were created in various tissues with the following SUV calculations: heart (maximum standardized uptake value [SUVMax] 8.60, mean standardized uptake value [SUVMean] 5.42), thymus (SUVMax 3.86, SUVMean 2.59), liver (SUVMax 1.37, SUVMean 0.99), right lung (SUVMax 0.92, SUVMean 0.56), and left lung (SUVMax 0.88, SUVMean 0.51). Sixty- to 90-minute uptake periods were sufficient to separate tissues based on background SUV activity. No gross differences in image quality were seen between intraperitoneal and intravenous injections of 18F-FDG. Respiratory gating also did not have a significant impact on image quality of lung parenchyma. The authors concluded that 18F-FDG PET and CT imaging can be performed successfully in normal healthy ferrets with the parameters identified in this study. They obtained similar imaging features and uptake measurements with and without respiratory gating as well as with intraperitoneal and intravenous 18F-FDG injections. 18F-FDG PET and CT can be a valuable resource for the in vivo tracking of disease progression in future studies that employ the ferret model.

Abstract 2439: Molecular imaging of spatial and temporal heterogeneity of tumor micro-environment in mouse models of non-small cell lung cancer macroscopic xenografts and micro-metastases

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL 18F-fluoro-2-deoxyglucose (18F-FDG, imaging glucose metabolism), 18F-fluorothymidine (18F-FLT, cell proliferation) and 18F-misonidazole (18F-FMISO, hypoxia) PET scans have emerged as important clinical tools for management of cancer. The objective of this study was to spatially and temporally visualize tumor microenvironment of tumor hypoxia, proliferation and glucose metabolism using 18F-FDG, 18F-FLT and 18F-FMISO digital autoradiography and microPET comparing with histological findings. Methods: We used human non-small cell lung cancer (NSCLC) A549 and HTB177 cells to generate subcutaneous and peritoneal metastases in nude mice. Animals were coinjected with the mixture of one PET radiotracer, pimonidazole (hypoxia marker) and bromodeoxyuridine (proliferation marker) intravenously 1 hour before animal euthanasia. The intratumoral distributions of radiotracers were visualized by digital autoradiography (DAR) and related to microscopic visualization of cellular proliferation, tumor hypoxia, stroma and necrosis. Serial microPET scans (day 1to day5) were also performed in the same animals to investigate change in glucose metabolism (using 18F-FDG), proliferation (18F-FLT) and hypoxia (18F-FMISO). Results: NSCLC microenvironment was complex and highly heterogeneous: xenografts had complex structures with intermingled regions of well oxygenated (negative pimonidazole) and highly proliferative (positive bromodeoxyuridine) cancer cells, hypoxic (positive pimonidazole) and low proliferation (little bromodeoxyuridine) cancer cells stroma and necrosis. Hypoxic cancer cells had high18F-FDG and 18F-FMISO but low 18F-FLT accumulation, indicating increased glucose metabolism is not a common feature of cancer cells but only hypoxic ones. Well oxygenated cancer cells with high proliferation rate accumulated high level of 18F-FLT, but low 18F-FDG and18F-FMISO. Stroma and necrotic zones always associated with low activity in all radiotracers we tested. MicroPET scans revealed apparent change in intratumor distribution of 18F-FLT, 18F-FDG as well as 18F-FMISO in as short as ∼48 hrs interval, indicating temporal heterogeneity of tumor microenvironment in term of proliferation, glucose metabolism and hypoxia. Conclusions: Both macroscopic xenografts and micrometastases of NSCLC have spatial heterogeneity of tumor microenvironment. Temporal change of tumor microenvironment did occur in a very short of interval of natural growth process in NSCLC. We have investigated to spatial and temporal behavior of heterogeneity of tumor microenvironment which is important for better understanding cancer biology and cancer management, if our findings in mice models are clinically applicable. Acknowledgement: This study was supported by Kentucky Lung Cancer Research Program Award to Dr. Xiao-Feng Li. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2439. doi:1538-7445.AM2012-2439