Quantification of [11C]yohimbine binding to α2 adrenoceptors in rat brain in vivo
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Quantification of [11C]yohimbine binding to α2 adrenoceptors in rat brain in vivo. / Phan, Jenny-Ann; Landau, Anne M.; Wong, Dean F.; Jakobsen, Steen; Nahimi, Adjmal; Doudet, Doris J.; Gjedde, Albert.
In: Journal of Cerebral Blood Flow and Metabolism, Vol. 35, No. 3, 03.2015, p. 501-511.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Quantification of [11C]yohimbine binding to α2 adrenoceptors in rat brain in vivo
AU - Phan, Jenny-Ann
AU - Landau, Anne M.
AU - Wong, Dean F.
AU - Jakobsen, Steen
AU - Nahimi, Adjmal
AU - Doudet, Doris J.
AU - Gjedde, Albert
PY - 2015/3
Y1 - 2015/3
N2 - We quantified the binding potentials (BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ∼38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.
AB - We quantified the binding potentials (BPND) of [11C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [11C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [11C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [11C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [11C]yohimbine BPND of ∼38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [11C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.
KW - [C-11]yohimbine
KW - alpha-2 adrenoceptors
KW - amphetamine challenge
KW - Inhibition plot
KW - reference region
U2 - 10.1038/jcbfm.2014.225
DO - 10.1038/jcbfm.2014.225
M3 - Journal article
C2 - 25564241
VL - 35
SP - 501
EP - 511
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
SN - 0271-678X
IS - 3
ER -
ID: 160924580