Mapping α2 Adrenoceptors of the Human Brain with 11C-Yohimbine
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Mapping α2 Adrenoceptors of the Human Brain with 11C-Yohimbine. / Nahimi, Adjmal; Jakobsen, Steen; Munk, Ole L.; Vang, Kim; Phan, Jenny A.; Rodell, Anders; Gjedde, Albert.
In: Journal of Nuclear Medicine, Vol. 56, No. 3, 03.2015, p. 392-398.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Mapping α2 Adrenoceptors of the Human Brain with 11C-Yohimbine
AU - Nahimi, Adjmal
AU - Jakobsen, Steen
AU - Munk, Ole L.
AU - Vang, Kim
AU - Phan, Jenny A.
AU - Rodell, Anders
AU - Gjedde, Albert
PY - 2015/3
Y1 - 2015/3
N2 - A previous study from this laboratory suggested that 11C-yohimbine, a selective α2-adrenoceptor antagonist, is an appropriate ligand for PET of α2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood–brain clearances, volumes of distribution, and receptor availability by means of PET with 11C-yohimbine in healthy male adults. Methods: We recorded the distribution of 11C-yohimbine with 90-min dynamic PET and sampled arterial blood to measure intact 11C-yohimbine in plasma. For analysis, we coregistered PET images to individual MR images and automatically identified 27 volumes of interest. We used 1-tissue-compartment graphical analysis with 6 linearized solutions of the fundamental binding equation, with the metabolite-corrected arterial plasma curves as input function, to estimate the kinetic parameters of 11C-yohimbine. With the lowest steady-state distribution volume (VT), determined in the corpus callosum, we calculated the binding potential (receptor availability) of the radioligand in other regions. Results: The linear regressions yielded similar estimates of the kinetic parameters. The cortical values of VT ranged from 0.82 mL cm−3 in the right frontal cortex to 0.46 mL cm−3 in the corpus callosum, with intermediate VT values in subcortical structures. Binding potentials averaged 0.6–0.8 in the cortex and 0.2–0.5 in subcortical regions. Conclusion: The maps of 11C-yohimbine binding to α2 adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer 11C-yohimbine for mapping α2 adrenoceptors in human brain in vivo.
AB - A previous study from this laboratory suggested that 11C-yohimbine, a selective α2-adrenoceptor antagonist, is an appropriate ligand for PET of α2 adrenoceptors that passes readily from blood to brain tissue in pigs but not in rodents. To test usefulness in humans, we determined blood–brain clearances, volumes of distribution, and receptor availability by means of PET with 11C-yohimbine in healthy male adults. Methods: We recorded the distribution of 11C-yohimbine with 90-min dynamic PET and sampled arterial blood to measure intact 11C-yohimbine in plasma. For analysis, we coregistered PET images to individual MR images and automatically identified 27 volumes of interest. We used 1-tissue-compartment graphical analysis with 6 linearized solutions of the fundamental binding equation, with the metabolite-corrected arterial plasma curves as input function, to estimate the kinetic parameters of 11C-yohimbine. With the lowest steady-state distribution volume (VT), determined in the corpus callosum, we calculated the binding potential (receptor availability) of the radioligand in other regions. Results: The linear regressions yielded similar estimates of the kinetic parameters. The cortical values of VT ranged from 0.82 mL cm−3 in the right frontal cortex to 0.46 mL cm−3 in the corpus callosum, with intermediate VT values in subcortical structures. Binding potentials averaged 0.6–0.8 in the cortex and 0.2–0.5 in subcortical regions. Conclusion: The maps of 11C-yohimbine binding to α2 adrenoceptors in human brain had the highest values in cortical areas and hippocampus, with moderate values in subcortical structures, as found also in vitro. The results confirm the usefulness of the tracer 11C-yohimbine for mapping α2 adrenoceptors in human brain in vivo.
KW - C-11-yohimbine
KW - alpha(2) adrenoceptors
KW - positron emission tomography
KW - brain
KW - noradrenaline
U2 - 10.2967/jnumed.114.145565
DO - 10.2967/jnumed.114.145565
M3 - Journal article
C2 - 25635132
VL - 56
SP - 392
EP - 398
JO - The Journal of Nuclear Medicine
JF - The Journal of Nuclear Medicine
SN - 0161-5505
IS - 3
ER -
ID: 160931508