Abstract
Accurate live tumor imaging in mice is now possible by means of high-resolution positron emission tomography (micro-PET) and X-ray computed tomography (micro-CT). By providing a powerful tool to examine biological samples with complex structure in vivo, this technology generated a significant advance in the cancer research field, particularly regarding the ability to perform longitudinal studies in combination with a therapeutic intervention. Here, we describe methods to optimize visualization of murine lung tumors by micro-PET, micro-CT and combined micro-PET-CT.
Keywords: Cancer, Imaging, CT, Lung cancer
Part I. Imaging by positron emission tomography (micro-PET) The imaging of tumors at inner body locations in living animals is more challenging than the imaging of subcutaneous tumors. We have optimized the procedures outlined in the following protocol in order to study lung tumors in genetically modified mice and orthotopic models. Briefly, the mice are anesthetized prior to the administration of the [18F]-Fluorodeoxigluycose (18F-FDG) dose, and kept under anesthesia during the whole period of probe uptake and imaging, ensuring at all times that the mice are warm. The standardization of mouse handling and of anesthesia usage is essential to ensure data reproducibility and comparability.
Materials and Reagents
Equipment
Software
Procedure
Part II. Imaging by Computed Tomography (micro-CT) Micro-CT studies are simpler than micro-PET since micro-CT requires little or no preparation. However, mice must be immobilized under anesthetics to avoid artifacts arising from movement. Likewise, in order to prevent anesthesia-induced hypothermia mice must be maintained at constant body temperature by means of a heating pad. Exogenous contrast agents are often used to improve the signal ratio between the tumor and the surrounding healthy tissue, but for the detection of lung tumors contrast is not required.
Part III. Imaging by multimodality (micro-PET-CT) The immobilization of mice during the exploration is essential for image co-registration in multimodality imaging studies. If positions during micro-PET and micro-CT studies are different, the matching (co-registration) of the images obtained by micro-PET and micro-CT is not possible.
Acknowledgments
This protocol has been adapted from the previously published study “Imaging Cancer in Mice by PET, CT, and Combined PET-CT” (Mulero et al., 2011). We are grateful to the Molecular Imaging Core Unit for the expertise and key contributions to the optimization of the protocols described here. This work was supported by grants from the CDTI (Spanish center of industrial and technological development Spanish Ministry of Science), AMIT Project “Advanced Molecular Imaging technologies” (5710001425) to FM. CA is the recipient of a postdoctoral fellowship from the Spanish Association Against Cancer (AECC).
References
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