Abstract
Progress in neuroscience research often involves animals, as no adequate alternatives exist to animal models of living systems. However, both the physiological characteristics of the species used and the effects of anesthesia raise questions of common concern. Here, we demonstrate the confounding influences of these effects on tracer binding in positron emission tomography (PET). We determined the effects of two routinely used anesthetics (isoflurane and propofol) on the binding of two tracers of monoamine function, [11C]SCH23390, a tracer of the dopamine D1 and D5 receptors, and the alpha2-adrenoceptor antagonist, [11C]yohimbine, in Göttingen minipigs. The kinetics of SCH23390 in the pigs differed from those of our earlier studies in primates. With two different graphical analyses of uptake of SCH23390, the initial clearance values of this tracer were higher with isoflurane than with propofol anesthesia, indicative of differences in blood flow, whereas no significant differences were observed for the volumes of distribution of yohimbine. The study underscores the importance of differences of anesthesia and species when the properties of radioligands are evaluated under different circumstances that may affect blood flow and tracer uptake. These differences must be considered in the choice of a particular animal species and mode of anesthesia for a particular application.
Highlights
Animals often serve as models of human diseases and pharmacological challenges
We demonstrate the confounding influences of these effects on tracer binding in positron emission tomography (PET)
The heart rate was higher for isoflurane-anesthetized minipigs than for propofol-anesthetized minipigs throughout the course of the study (P = 0.0078)
Summary
Animals often serve as models of human diseases and pharmacological challenges. This practice includes the evaluation of the use of new radioligands for the study of conditions of relevance to the human population. The search for the most appropriate animal models is driven by multiple considerations of time, species, size, and cost of acquisition. For brain imaging such as positron emission tomography (PET), the size of the brain and the resolution of specific brain structures become important. BioMed Research International for preclinical studies, or for the development of new tracers for human use, to the extent that they influence data analysis and interpretation. Among these factors, effects of anesthesia and specific physiological characteristics of the species can vary between humans and animals and play a role. Most in vivo imaging depends on anesthesia to ensure immobility and reproducibility in long or multiple tracer imaging protocols
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