A positron emission tomograph and microCT for small animal imaging

Positron emission tomography is a unique imaging modality providing quantitative data on cell-cell communication, tissue function and metabolism. PET scanners for clinical use have fields-of-view of 55 cm diameter and 16 cm axial length. Such scanners are optimal for studies in patients, but their spatial resolution (5 mm FWHM) is not sufficient for research in laboratory animals. Dedicated PET systems with a smaller field-of-view and superior resolution (1-2 mm FWHM) have recently become available, allowing in vivo studies in rodents. Improved resolution is the result of a newly designed detector unit using lutetium orthosilicate (LSO) as scintillator in combination with position-sensitive photomultiplier tubes. The smaller field-of-view of these scanners results in superior sensitivity (because of a larger effective solid angle). Combination of an animal PET camera with a microCT allows image fusion. In combined microPET-microCT images (40µ resolution), the anatomical origin of the PET signals is clearly visible. This exciting new development in PET technology has opened a whole spectrum of possibilities for preclinical research: 1.Serial, noninvasive measurements are possible in a single rodent which functions as its own. control. Longitudinal studies can therefore be performed with small numbers of animals and with excellent statistical quality of the data. 2. Positron-emitting radiotracers have recently been developed to visualize protein-protein interactions, second messenger systems, angiogenesis, apoptosis and markers for neurodegeneration like ß-amyloid plaques and neurofibrillary tangles. Animal PET will therefore stimulate research on tumor therapy and on the treatment of neurodegenerative diseases. Furthermore, established tracers are available for neuroreceptors, transporters and enzymes, blood flow and metabolism. Animal PET makes it possible to apply these tracers in rodents and therefore has a large potential impact in basic brain research, cardiology and tumor biology. State-of-the-art research institutions will make an increasing use of small animal imaging. 3. Increased availability of animal models of human disease has stimulated basic research on pathophysiology and studies of drug therapy in mice and rats. In these models, PET is useful for quantification of the pharmacokinetics and functional effects of drugs. 4. The high specific radioactivity of positron emitting radionuclides not only permits quantitative study of biochemical processes via a tracer approach, but also ex vivo labeling of intact cells and subsequent monitoring of their trafficking within the body. Basic research on the behavior of stem cells and of inflammatory cells will therefore greatly benefit from animal PET technology. 5. Gene therapy of human disease is hampered by lack of information on the location, magnitude and duration of ectopic gene expression following DNA delivery. Noninvasive PET assays of the gene product(s) in animal models of disease will thus be essential for preclinical optimizatlon of gene therapy protocols. Several research groups within the Medical Faculty and the Faculty for Mathematics and Natural Sciences are active within the aforementioned fields of study. Particularly groups addressing stem cell research, tumor biology and basic neuroscience consider a facility for animal PET and microCT an important tool to support the quality of their research. Research groups from other universities within the Netherlands and from pharmaceutical companies have already access to the Groningen University PET center and are interested in use of the proposed animal scanners. We request funding to acquire and install a Concorde microPET Focus and microCT system within the PET center in Groningen. This will result in a facility for high-resolution PET/CT which is unique for the Netherlands. Personnel and infrastructure to maintain the facility and to coordinate the research is available.