Mapping α2 adrenoceptors of the human brain with11C-yohimbine

Adjmal Nahimi, Steen Jakobsen, Ole L. Munk, Kim Vang, Jenny A. Phan, Anders Rodell, Albert Gjedde

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)392-398
Number of pages7
JournalJournal of Nuclear Medicine
Volume56
Issue number3
DOIs
StatePublished - Mar 1 2015

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Yohimbine
Adrenergic Receptors
Brain
Corpus Callosum
Frontal Lobe
Rodentia
Linear Models
Hippocampus
Swine
Ligands

Keywords

  • <sup>11</sup>c-yohimbine
  • Brain
  • Noradrenaline
  • Positron emission tomography
  • α<inf>2</inf> adrenoceptors

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

Cite this

Nahimi, A., Jakobsen, S., Munk, O. L., Vang, K., Phan, J. A., Rodell, A., & Gjedde, A. (2015). Mapping α2 adrenoceptors of the human brain with11C-yohimbine. Journal of Nuclear Medicine, 56(3), 392-398. https://doi.org/10.2967/jnumed.114.145565

Mapping α2 adrenoceptors of the human brain with11C-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, 01.03.2015, p. 392-398.

Research output: Contribution to journalArticle

Nahimi, A, Jakobsen, S, Munk, OL, Vang, K, Phan, JA, Rodell, A & Gjedde, A 2015, 'Mapping α2 adrenoceptors of the human brain with11C-yohimbine', Journal of Nuclear Medicine, vol. 56, no. 3, pp. 392-398. https://doi.org/10.2967/jnumed.114.145565
Nahimi A, Jakobsen S, Munk OL, Vang K, Phan JA, Rodell A et al. Mapping α2 adrenoceptors of the human brain with11C-yohimbine. Journal of Nuclear Medicine. 2015 Mar 1;56(3):392-398. https://doi.org/10.2967/jnumed.114.145565
Nahimi, Adjmal ; Jakobsen, Steen ; Munk, Ole L. ; Vang, Kim ; Phan, Jenny A. ; Rodell, Anders ; Gjedde, Albert. / Mapping α2 adrenoceptors of the human brain with11C-yohimbine. In: Journal of Nuclear Medicine. 2015 ; Vol. 56, No. 3. pp. 392-398.
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abstract = "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.",
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