Impact of inherent variability and experimental parameters on the reliability of small animal PET data

Brain standardized uptake values of rodents were compared between three PET scans of the same animal and scans of different individuals. 18F-FDG ex vivo tissue sampling was performed under variation of the following experimental parameters: gender, age, cage occupancy, anesthetic protocol, environmental temperature during uptake phase, and tracer formulation.No significant difference of variability in 18F-FDG or 18F-fallypride brain or striatal uptake was identified between scans of the same and scans of different animals (COV？=？14？±？7% vs. 21？±？10% for 18F-FDG). 18F-FDG brain uptake was robust regarding a variety of experimental parameters; only anesthetic protocols showed a significant impact. In contrast to a heterogenization approach, homogenization of groups produced more false positive effects in 18F-FDG organ distribution showing a false positive rate of 9% vs. 6%.Repeated measurements of the same animal may not reduce data variability compared with measurements on different animals. Controlled heterogenization of test groups with regard to experimental parameters is advisable as it decreases the generation of false positive results and thus increases external validity of study outcome.Small animal positron emission tomography (PET) is a frequently used methodology to investigate rodent models of healthy and diseased states. Preclinical PET has been revolutionized with the development of dedicated small animal PET scanners [1-3]. Noninvasive imaging methods such as PET are considered to give more reliable results in longitudinal follow-up studies where animals can be used as their own control compared with studies where test and control animals are not identical [1,4]. Additionally, strict homogenization of experimental parameters reduces variability within test groups and is therefore believed to increase reliability of animal experiments [5,6]. Nevertheless, recent investigations on mouse behavior revealed that the rate of false positive outcome was signifi