RT Journal Article
SR Electronic
T1 Mapping α<sub>2</sub> Adrenoceptors of the Human Brain with <sup>11</sup>C-Yohimbine
JF Journal of Nuclear Medicine
JO J Nucl Med
FD Society of Nuclear Medicine
SP 392
OP 398
DO 10.2967/jnumed.114.145565
VO 56
IS 3
A1 Adjmal Nahimi
A1 Steen Jakobsen
A1 Ole L. Munk
A1 Kim Vang
A1 Jenny A. Phan
A1 Anders Rodell
A1 Albert Gjedde
YR 2015
UL http://jnm.snmjournals.org/content/56/3/392.abstract
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.