Binding characteristics and sensitivity to endogenous dopamine of [¹¹C]‐(+)‐PHNO, a new agonist radiotracer for imaging the high‐affinity state of D₂ receptors in vivo using positron emission tomography

Abstract

[ 11 C]-(+)-PHNO (4-propyl-9-hydroxynaphthoxazine) is a newagonist radioligand that provides a unique opportunity to measure the high-affinity states of the D 2 receptors (D 2 -high) using positron emission tomography (PET). Here we report on the distribution, displaceablity, specificity and modeling of

Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [11C](+)PHNO

“…Without utilizing a pharmacologic intervention such as the tyrosine-hydroxylase inhibitor α-methly-para-tyrosine (AMPT) to deplete tonic dopamine (Abi-Dargham et al, 2000;Caravaggio et al, 2014;Laruelle et al, 1997;Martinez et al, 2009), our outcome measure, BP ND , reflects tracer bound to receptors not currently occupied by the endogenous neurotransmitter (ie, dopamine) and therefore measures receptor availability (Innis et al, 2007). [ 11 C](+)PHNO has been shown to be substantially more sensitive to endogenous dopamine competition (ie, increased tracer displacement resulting in lower BP ND ) compared with the antagonist tracers used in prior studies (Cropley et al, 2008;Gallezot et al, 2014a;Ginovart et al, 2006;Moerlein et al, 1997;Shotbolt et al, 2012;Willeit et al, 2008); thus, our receptor availability findings could also be due to OB individuals exhibiting lower levels of tonic dopamine. In fact, this concept is consistent with prior reports that have shown dietinduced OB and OB-prone rats exhibited lower levels of tonic dopamine or less dopaminergic-mediated behaviors (ie, conditioned place preference or amphetamine-induced locomotor activity) compared with standard chow fed or OB-resistant controls (Geiger et al, 2009;Hryhorczuk et al, 2016;Rada et al, 2010).…”

Measuring Endogenous 5-HT Release by Emission Tomography: Promises and Pitfalls

“…The relative merits of radioligands such as raclopride, IBZM, and NPA that render them sensitive to displacement by endogenous dopamine in which other D2 ligands are not remains unclear. It does not seem to involve affinity, pharmacological action (agonist versus antagonist), or lipophilicity, but may involve chemical structure (Laruelle, 2000;Ginovart et al, 2006). Specific binding of a radiotracer is a function of its affinity for the site relative to the density (B max ) of that binding site.…”

Neuroimaging in Parkinson's Disease

“…In contrast, [ 11 C]raclopride has a lower affinity, and its binding is accordingly affected by changes in the availability of synaptic DA [45,46]. This can be used to advantage to estimate DA release in response to a variety of pharmacological [47,48], physical [49][50][51], or behavioral [52][53][54] C-labeled PHNO [64] may be used to estimate changes in synaptic DA. Because of its relative selectivity, PHNO may also be useful for visualizing dopamine D3 receptors.…”