Evaluation of [18F]fluoroxanomeline {5-{4-[(6-[18F]fluorohexyl)oxy]-1,2,5-thiadiazol-3-yl}-1-methyl-1,2,3,6-tetrahydropyridine} in muscarinic knockout mice

Nuclear Medicine and Biology
Dale O KiesewetterWilliam C Eckelman


We set out to develop a muscarinic M1-selective agonist (based on the structure of the functionally M1-selective xanomeline) that could be radiolabeled with fluorine-18 for use as an imaging agent for positron emission tomography. The radiochemical synthesis was achieved, employing the arts of organic and radiochemical syntheses. Binding selectivity studies employed biodistribution studies, using autoradiography and/or tissue dissection, in wild-type or muscarinic receptor knockout mice. [(18)F]Fluoroxanomeline shows rather uniform uptake in all mouse brain regions and high specific binding, with a brain-to-blood ratio of 32 at 60 min postinjection. In addition, the specific binding is demonstrated by a 58% to 75% decrease in brain uptake upon coinjection with 5 nmol of unlabeled fluoroxanomeline or xanomeline. Brain uptake studies with [(3)H]xanomeline in muscarinic knockout mice show decreased uptake in M1 (17-34%) and M2 (2-20%) knockout mice compared with control. However, statistical significance was observed in only a few regions. Comparison of [(18)F]fluoroxanomeline in knockout mice showed no difference in M1 or M4 knockout mice but a general decrease in M2 (2-24%) knockout mice. The decrease of [(18)F]fluoroxanomeline ...Continue Reading


Jan 1, 1985·International Journal of Nuclear Medicine and Biology·R E GibsonR Eng
May 1, 1973·The Journal of Pharmacy and Pharmacology·T D InchP B Thompson
Apr 1, 1984·Journal of Pharmaceutical Sciences·William C EckelmanR C Reba
Jan 1, 1995·Molecular and Chemical Neuropathology·G Ferrari-DiLeoD D Flynn
Jan 6, 1995·Journal of Medicinal Chemistry·Dale O KiesewetterWilliam C Eckelman
Jan 1, 1993·Life Sciences·R D SchwarzA J Thomas
Jan 12, 1999·British Journal of Pharmacology·J WatsonA M Brown
Feb 17, 1999·Proceedings of the National Academy of Sciences of the United States of America·J GomezaJ Wess
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·J GomezaJ Wess
Apr 6, 2000·The Journal of Biological Chemistry·J JakubikS Tucek
Nov 4, 2000·Expert Opinion on Investigational Drugs·A D Korczyn
Dec 29, 2000·Japanese Journal of Pharmacology·A Fisher
Feb 24, 2001·European Journal of Nuclear Medicine·K NobuharaG Sedvall
Aug 2, 2001·Trends in Pharmacological Sciences·R M EglenN Watson
Sep 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·S K Hemrick-LueckeC C Felder
Jun 12, 2003·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Thomas J RaedlerDaniel R Weinberger
Jul 23, 2003·Trends in Pharmacological Sciences·Terry Kenakin
May 23, 2006·Current Topics in Medicinal Chemistry·Alexandre CoimbraEric D Hostetler

Related Concepts

Total Body Clearance Rate
Tissue Specificity
Muscarinic Acetylcholine Receptor
Drug or Chemical Tissue Distribution
Mice, Knockout

Related Feeds

Alzheimer's Disease: Neuroimaging

Neuroimaging can help identify pathological hallmarks of Alzheimer's disease (AD). Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.

Basal Forebrain- Circuits

Basal forebrain is a region in the brain important for production of acetylcholine and is the major cholinergic output of the CNS. Discover the latest research on circuits in the basal forebrain here.