Radiosynthesis and biodistribution of a histamine H3 receptor antagonist 4-[3-(4-piperidin-1-yl-but-1-ynyl)-[11C]benzyl]-morpholine: evaluation of a potential PET ligand

Anu J. Airaksinen, Jill A. Jablonowski, Margreet van der Mey, Ann J. Barbier, Rob P. Klok, Joost Verbeek, Robert Schuit, Jacobus D.M. Herscheid, Josee E. Leysen, Nicholas I. Carruthers, Adriaan A. Lammertsma, Albert D. Windhorst

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)


The potent histamine H3 receptor antagonist JNJ-10181457 (1) was successfully labeled with 11C in a novel one-pot reaction sequence, with high chemical yield (decay-corrected yield, 28±8%) and high specific radioactivity (56±26 GBq/μmol). The binding of [11C]1 to H3 receptors was studied in vitro in rat brain and in vivo in rats and mice. The in vitro binding of [11C]1 in rat coronal brain slices showed high binding in the striatum, and this binding was blocked by histamine and by two known H3 antagonists, JNJ-5207852 (2) and unlabeled Compound (1), in a concentration-dependent manner. The biodistribution of [11C]1 in rats was measured at 5, 10, 30 and 60 min. The uptake of [11C]1 in regions rich in H3 receptors was highest at 30 min, giving 0.98%, 1.41%, 1.28% and 1.72% dose/g for the olfactory bulb, hippocampus, striatum and cerebral cortex, respectively. However, the binding of [11C]1 in the rat brain could not be blocked by pretreatment with either Compound (2) (30 min or 24 h pretreatment) or cold Compound (1) (30-min pretreatment). The biodistribution of [11C]1 in a second species (Balb/c mice) showed a higher overall uptake of the radioligand with an average brain uptake of 8.9% dose/g. In C57BL/6-H3(-/-) knockout mice, a higher brain uptake was also observed. Analyses of metabolites and plasma protein binding were also undertaken. It appeared that [11C]1 could not specifically label H3 receptors in rodent brain in vivo. Possible causes are discussed.

Original languageEnglish
Pages (from-to)801-810
Number of pages10
JournalNuclear medicine and biology
Issue number6
Publication statusPublished - 1 Aug 2006


  • Antagonist
  • Autoradiography
  • Biodistribution
  • Brain
  • Histamine H receptor
  • PET ligand

Cite this