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Technical Sheet MRI and PET in Small and Large Animals as Additional Endpoints to Toxicology Studies Magnetic resonance imaging (MRI) and positron emission tomography (PET) are now part of Charles River’s toxicology services. The Sherbrooke site offers these imaging modalities in partnership with the Sherbrooke Molecular Imaging Center (CIMS) within the Research Center of the Sherbrooke University Hospital (CRCHUS) as additional endpoints to toxicology studies. Contrary to traditional methods, MRI and PET imaging provide complementary, precise in vivo data noninvasively, allowing real-time processes to be investigated. They also enable monitoring of a pathological state over time. MRI and PET are both major translational imaging tools for drug discovery across multiple disease areas, such as the platform used at Charles River Finland to evaluate central nervous system (CNS) disease. Use of these powerful tools in drug development provides a significant enhancement to the safety assessment of novel molecules. Furthermore, MR and PET images can be co-registered, increasing the power of data provided by these two modalities. Magnetic Resonance Imaging (MRI) MRI is a unique noninvasive method generating high resolution images, which give particularly precious anatomical and structural information. The Sherbrooke Molecular Imaging Center is equipped with two MRI magnets: one for small animals and one for large animals. Clients have the opportunity to enhance their toxicology study with MRI. This technology can be a useful tool for the characterization of tumors (i.e., volume, permeability) and the assessment of the heart function (i.e., ventricular ejection fraction). Furthermore, MRI enables the evaluation of adverse effects on brain morphology (i.e., regional brain atrophy and cortical thickness), axonal networks (i.e., white matter integrity and brain connectivity) and neuronal activation relative to a toxicology study. Small animals Large animals Magnet 7.0 Tesla 3.0 Tesla Supplier Varian Philips Isotropic resolution 0.1 mm 1.0 mm Functionality: • Anatomical MRI -- Conventional static T1 and T2 weighted images -- Dynamic contrast-enhanced (DCE) acquisitions (with contrast agents) -- Pharmacokinetic analysis • Diffusion MRI (tractography) • Functional MRI (air puff BOLD) Figure 1. MRI 3 Tesla Philips Figure 2. Rat heart image generated on the 7 Tesla MRI by Dr. Luc Tremblay [email protected] www.criver.com © 2015, Charles River Laboratories International, Inc. Positron Emission Tomography (PET) PET is an imaging method generating functional and metabolic images. It has the power to image the three-dimensional distribution of specialized radio-labeled compounds. The Sherbrooke Molecular Imaging Center is equipped with two small-animal PET scanners, presented in the table below. This technology is useful in discovery for the characterization of tumors (i.e., glucose uptake, quantification of estrogen receptors and cell proliferation), brain function (i.e., dopaminergic system functionality, glucose uptake and amyloid-b deposition) and metabolic problems (i.e., heart fatty acid uptake and thyroid dysfunction). Similar endpoints would be informative when added to ongoing toxicology studies. LabPET4 Triumph Axial field of view 4 cm 7.5 cm (allowing mouse whole-body imaging) Isotropic spatial resolution 1.2 mm 1.2 mm Additional device - Computed tomography (CT) scanner integrated By increasing the efficiency of preclinical phases, MRI and PET imaging have the potential to considerably reduce the time and costs of bringing a drug to market. With both modalities being routinely used in humans, the translation from preclinical to clinical phases is easily facilitated, and with the ongoing technological advancement of MRI and PET imaging, the power of preclinical imaging will continue to grow. Figure 3. LabPET4 PET scanner Figure 4. Mouse wholebody PET-CT scan image generated by Jean-François Beaudoin Functionality: • Radiotracer uptake/metabolism (dual tracer protocols possible) • 18F, 15O, 13N, 11C, 64Cu-labeled tracers: 18F-FDG, 18F-FTHA, 18F-FLT, 18F-DOPA, 11C-PIB, H215O, 11C-acetate, 11C-acetoacetate • Dynamic acquisitions and kinetic modeling (with quantitative measures) • Receptor/transporter occupancy • Biodistribution (tracers and drugs) • Real-time therapy evaluation [email protected] www.criver.com © 2015, Charles River Laboratories International, Inc.
