TY - JOUR

T1 - Effects of anesthesia and species on the uptake or binding of radioligands in vivo in the Göttingen minipig

AU - Alstrup, Aage Kristian Olsen

AU - Landau, Anne M.

AU - Holden, James E.

AU - Jakobsen, Steen

AU - Schacht, Anna C.

AU - Audrain, Helene

AU - Wegener, Gregers

AU - Hansen, Axel Jacob Kornerup

AU - Gjedde, Albert

AU - Doudet, Doris

PY - 2013

Y1 - 2013

N2 - 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, [ C 11 ]SCH23390, a tracer of the dopamine D1 and D5 receptors, and the alpha2-adrenoceptor antagonist, [ C 11 ]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.

AB - 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, [ C 11 ]SCH23390, a tracer of the dopamine D1 and D5 receptors, and the alpha2-adrenoceptor antagonist, [ C 11 ]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.

U2 - 10.1155/2013/808713

DO - 10.1155/2013/808713

M3 - Journal article

C2 - 24083242

AN - SCOPUS:84884826070

VL - 2013

JO - BioMed Research International

JF - BioMed Research International

SN - 2314-6133

M1 - 808713

ER -