Synthesis and evaluation of inhaled [11C]butane and intravenously injected [11C]acetone as potential radiotracers for studying inhalant abuse

The phenomenon of inhalant abuse is a growing problem in the US and many countries around the world. Yet, relatively little is known about the pharmacokinetic properties of inhalants that underlie their abuse potential. While the synthesis of 11 C-labeled toluene, acetone and butane has been proposed in the literature, none of these compounds has been developed as radiotracers for PET studies. In the present report we extend our previous studies with [C-11]toluene to include [C-11]acetone and [11C]butane with the goal of comparing the pharmacokinetic profiles of these three volatile abused substances. Both [C-11]toluene and [C-11]acetone were administered intravenously and [C-11]butane was administered via inhalation to anesthesized baboons. Rapid and efficient uptake of radiolabeled toluene and acetone into the brain was followed by fast clearance in the case of toluene and slower kinetics in the case of acetone. [C-11]Butane was detected in the blood and brain following inhalation, but the levels of radioactivity in both tissues dropped to half of the maximal values over the period of less than a minute. To our knowledge, this is the first reported study of the in vivo brain pharmacokinetics of labeled acetone and butane in nonhuman primates. These data provide insight into the pharmacokinetic features possibly associated with the abuse liability of toluene, acetone and butane. (c) 2005 Elsevier Inc. All rights reserved.