Imaging cortical dopamine D1 receptors using [11C]NNC112 and ketanserin blockade of the 5-HT 2A receptors - PubMed (original) (raw)

Imaging cortical dopamine D1 receptors using [11C]NNC112 and ketanserin blockade of the 5-HT 2A receptors

Ana M Catafau et al. J Cereb Blood Flow Metab. 2010 May.

Abstract

[(11)C]NNC112 (8-chloro-7-hydroxy-3-methyl-5-(7-benzofuranyl)-2,3,4,5-tetrahydro-IH-3-benzazepine), a selective positron-emission tomography (PET) ligand for the D(1) receptor (R) over the 5-HT(2A) R in vitro, has shown lower selectivity in vivo, hampering measurement of D(1) R in the cortex. [(11)C]NNC112 PET and intravenous (i.v) ketanserin challenge were used to (1) confirm the previous findings of [(11)C]NNC112 in vivo D(1) R selectivity, and (2) develop a feasible methodology for imaging cortical D(1) R without contamination by 5-HT(2A) R. Seven healthy volunteers underwent [(11)C]NNC112 PET scans at baseline and after a 5-HT(2A) R-blocking dose of ketanserin (0.15 mg/kg, i.v.). Percent BP(ND) change between the post-ketanserin and baseline scans was calculated. Irrespective of the quantification method used, ketanserin pretreatment led to significant decrease of BP(ND) in the cortical (approximately 30%) and limbic regions (approximately 20%) but not in the striatum, which contains a much lower amount of 5-HT(2A) R. Therefore, ketanserin allows D(1) R signal to be detected by [(11)C]NNC112 PET without significant 5-HT(2A) R contamination. These data confirm the presence of a significant 5-HT(2A) R contribution to cortical [(11)C]NNC112 signal, and call for caution in the interpretation of published [(11)C]NNC112 PET findings on cortical D(1) R in humans. In the absence of more selective ligands, [(11)C]NNC112 PET with ketanserin can be used for cortical D(1) R imaging in vivo.

PubMed Disclaimer

Figures

Figure 1

Figure 1

Co-registered MRI: [11C]NNC112 PET _BP_ND parametric images (mean from all subjects, _n_=6), at baseline (top) and after ketanserin 0.15 mg/kg, i.v. (bottom). The decrease of [11C]NNC112 signal in the cortical regions, without modification in the striatum, is appreciated.

Figure 2

Figure 2

T maps of _BP_ND change between baseline and post-ketanserin conditions. Threshold: P<0.001. A significant _BP_ND decrease was shown in the cortical areas, demonstrating [11C]NNC112 displacement from 5-HT2A R, whereas no significant changes are seen in the striatum (area devoid of 5-HT2A R).

Similar articles

Cited by

References

    1. Abi-Dargham A, Martinez D, Mawlawi O, Simpson N, Hwang DR, Slifstein M, Anjilvel S, Pidcock J, Guo NN, Lombardo I, Mann JJ, Van Heertum R, Foged C, Halldin C, Laruelle M. Measurement of striatal and extrastriatal dopamine D1 receptor binding potential with [11C]NNC 112 in humans: validation and reproducibility. J Cereb Blood Flow Metab. 2000;20:225–243. - PubMed
    1. Abi-Dargham A, Mawlawi O, Lombardo I, Gil R, Martinez D, Huang Y, Hwang DR, Keilp J, Kochan L, Van Heertum R, Gorman JM, Laruelle M. Prefrontal dopamine D1 receptors and working memory in schizophrenia. J Neurosci. 2002;22:3708–3719. - PMC - PubMed
    1. Andersen PH. Comparison of the pharmacological characteristics of [3H]raclopride and [3H]SCH 23390 binding to dopamine receptors in vivo in mouse brain. Eur J Pharmacol. 1988;146:113–120. - PubMed
    1. Andersen PH, Gronvald FC, Hohlweg R, Hansen LB, Guddal E, Braestrup C, Nielsen EB. NNC-112, NNC-687 and NNC-756, new selective and highly potent dopamine D1 receptor antagonists. Eur J Pharmacol. 1992;219:45–52. - PubMed
    1. Catafau AM, Danus M, Bullich S, Llop J, Perich J, Cunningham VJ, Plaza P, Penengo MM, Eersels JL, Squassante L, Ros D, Barbanoj M. Characterization of the SPECT 5-HT2A receptor ligand 123I-R91150 in healthy volunteers: part 1—pseudoequilibrium interval and quantification methods. J Nucl Med. 2006a;47:919–928. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources