Positron Emission Tomography: Updates on Imaging of Addiction

Abstract

FIGURE 1. A wide array of positron emission tomography (PET) ligands have been developed that provide information relevant to multiple aspects of addiction (1-3). Locations of targets are approximated on this diagram, which is color-coded by functional roles. On the presynaptic side (pink), targets include neurotransmitter precursors (orange, example [ 18 F]-fluorodopa, FDOPA), modulatory receptors (yellow, examples [ 11 C] GR103545, [ 11 C] LY27950509 and [ 18 F] LY2459989 for kappa opioid receptors, KOR; [ 18 F]FMPEP for cannabinoid 1 receptors, CB1), and neurotransmitter reuptake transporters (light green, examples [ 11 C] PE2I and [ 18 F] FE-PE2I for the dopamine transporter, DAT). On the postsynaptic side (purple), targets include neurotransmitter receptors (blue, examples [ 11 C] raclopride and [ 11 C]-(1)-PHNO for dopamine D 2 and D 3 receptors, D 2 R; [ 11 C] carfentanil for mu opioid receptors, MOR; [ 18 F] LY2459989 for both mu and kappa opioid receptors; 2-[ 18 F]fluoro-3-(2(S)-azetidinylmethoxy) pyridine for nicotinic acetylcholine receptors, nAChR). Some PET ligands target more generic functions.[ 18 F]-fluoro-deoxy-glucose (FDG) PET provides a measure of cerebral metabolic rate.

PET Imaging of [11C]MPC-6827, a Microtubule-Based Radiotracer in Non-Human Primate Brains

“…[3][4][5]. For example, the structural changes in neurons induced by alcohol contribute to the long-lasting nature of alcohol use disorder (AUD) [6][7][8]. Repeated exposure to alcohol induces structural plasticity [9,10] in brain reward circuits and changes in the density and morphology of dendritic spines, which have significant consequences including cognitive deficits [11].…”

“…Quantification of microtubules in vivo using PET (positron emission tomography) can provide significant information about altered disease mechanisms and can also be used evaluate therapeutic strategies to monitor the progress of treatment [8,23,24]. We screened multiple microtubule-targeting agents (MTAs) as potential PET ligands and identified MPC-6827 as our lead candidate [25].…”

“…However, microtubule structure and functions are sufficiently complex that the sequence of events from microtubule disruption to the expression of disease largely remains unknown [1,7,21,22]. Quantification of microtubules in vivo using PET (positron emission tomography) can provide significant information about altered disease mechanisms and can also be used evaluate therapeutic strategies to monitor the progress of treatment [8,23,24]. We screened multiple microtubule-targeting agents (MTAs) as potential PET ligands and identified MPC-6827 as our lead candidate [25].…”