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Klinik für Innere Medizin IHämatologie, Onkologie und Stammzelltransplantation

Animal Imaging Advisory Board

The Animal Imaging Advisory Board is a consulting service for preclinical imaging

The SFB 850 includes three different animal imaging modalities: Bioluminescence Imaging (BLI), Magnetic Resonance Imaging (MRI) and Positron Emission Imaging (PET). Each of this modality has some strengths and weaknesses. Therefore it will be challenging for the individual group leaders to decide which animal imaging modality is the best to answer their specific questions. The animal advisory board should be a forum which supports the project coordinators to define the best approach in respect to their specific requests

The imaging advisory board consists of one project coordinator from each modality.

MRI: Dr. Dominik v. Elverfeldt dominik.elverfeldt@uniklinik-freiburg.de
BLI: Prof. Dr. Robert Zeiser robert.zeiser@uniklinik-freiburg.de
PET: Dr. Martin Behe martin.behe@uniklinik-freiburg.de
  common e-mail: aiab@uniklinik-freiburg.de

The PI with interest in animal imaging needs to send the application sheet and a short abstract (about half a side) with the description of the request for an imaging application. The three members review it in a bimonthly meeting and give an advice to the applicant.

Table 1: Complementarity of the three imaging platforms

Method Advantage
BLI • Fast and low cost method for living animals
• High sensitivity
• Evaluating the kinetics of cell division is possible (signal intensity increases)
• Small cell populations can be detected (as little as 1000 cells in superficial areas)
• The presence of bioluminescence signal indicates that the luc+ cell population is viable
• Luciferase can be used as reporter-probe to monitor promoter activity of a gene of interest
MRI • Highest spatial resolution (< 100 µm )
• Directly translational to human application
• Combines multi contrast 3D morphological with multi modal functional imaging.
(e.g. Diffusion, Flow, fMRI, DCE-MRI and other)
• Passive, active and activatable contrast agents possible
PET • High sensitivity (pM)
• High tissue penetration (no limit in small animals)
• Three-dimensional images with high temporal (s) and reasonable spatial resolution (1-2 mm)
• Signal is linearly related to the concentration of the imaging probe allowing quantitative analysis
• Visualization and quantification of drug targets in living animals
• Quantitative studies of the pharmacokinetics of peptides and proteins of interest
• Evaluation of the metabolic and functional state of cells using a variety of established imaging probes without need of genetic engineering

In vivo Bioluminescence Imaging (BLI)

Luciferase-based imaging methods have been recently applied to detect widespread metastasis in different murine tumour models including breast cancer, prostate cancer, ovarian cancer, B cell lymphoma and other entities. BLI is of enormous advantage when small cell populations need to be isolated since it can provide guidance which anatomical regions need to be removed for further analysis. When luc transgenic cells are employed BLI is permissive for cell proliferation analysis since the reporter gene is duplicated upon cell division and thus signal intensity correlates with cell number. Combination of Luc expression and GFP expression in tumor cells allows further purification and analysis of tumor cell by FACS after BLI guided in vivo monitoring and recovery

Sequential bioluminescence imaging displays the metastatic pattern of ovarian cancer cells in immunocompetent mice (data from AG Zeiser).

Nuclear Magnetic Resonance Imaging (MRI)

The ability to generate multiple contrasts non invasively and at high resolution including various functional contrasts has given MRI an important role in clinical diagnostic imaging. These techniques have been translated to dedicated animal systems. Small animal MR is therefore already extensively used in preclinical oncology research, and its impact is growing as in addition to morphology and volumetry numerous processes can be quantitatively imaged. Numerous studies have for example shown the use of MR for measurements of perfusion and permeability by of tissue using DCE-MRI. Diffusion MR has been shown to be effective to control tumor response and to monitor apoptosis. 1H-, 31P- and 13C- spectroscopy has been extensively used to observe tumor metabolism. Currently, rapid progress is being made in the development of molecular probes to observe specific receptors as well as migration of iron oxide or 19F labeled cells. Combined application of parametric measurements has been shown to be a promising tool for therapeutic monitoring and imaging phenotyping of animal models.

Axial MRI images of the abdomen in a nude mouse. Displayed are a diffusion weighted image (left) and a T2-weighted image (right). The detection of a liver metastasis after intra-pancreatic injection of genetically modified tumor cells (data from AG Hennig/Elverfeldt)

Imaging of changes in tumour cell invasiveness during treatment with the src kinase inhibitor dasatinib using PET with 64Cu labelled RGD peptides (Data from AG Weber/Behe).

Positron emission tomography (PET)

PET allows monitoring morphology, physiology, function and metabolism in both preclinical and clinical studies. Small animal Positron-emission-tomography (PET) offers the possibility to visualize non-invasively and quantitatively the expression and function of biomolecules. This technique is therefore ideally suited for translational research. Tumor growth and the proliferation of metastasis can be monitored in longitudinal studies on single animals. In addition to morphological and anatomical information PET allows the visualization and quantification of biochemical processes.