PMID: 9468027Feb 19, 1998Paper

Synthesis and biological evaluation of [11C]MK-912 as an alpha2-adrenergic receptor radioligand for PET studies

Nuclear Medicine and Biology
C ShiueD B Bylund

Abstract

In vitro studies showed that MK-912 ((2S, 12bS)1',3'-dimethylspiro(1,3,4,5',6,6',7,12b-octahydro -2H-benzo[b]furo[2,3-a]quinolizine)-2,4'-pyrimidin-2'-one) is a potent alpha2-adrenergic receptor antagonist with high affinity (Ki = 0.42, 0.26 and 0.03 nM to alpha2A, alpha2B and alpha2C, respectively) and high selectivity (alpha2A/alpha1A = 240; alpha2A/D-1 = 3600; alpha2A/D-2 = 3500; alpha2A/5-HT1 = 700; alpha2A/5-HT2 = 4100). The compound was labeled with 11C and evaluated in rodents and monkey as a specific radioligand for studying alpha2-adrenergic receptors using PET. [11C]MK-912 was synthesized by methylation of its desmethyl precursor, L-668,929, with [11C]CH3I in (Bu3O)P=O at 85 degrees C for 8 min followed by purification with HPLC in 18% yield in a synthesis time of 45 min from end of bombardment (EOB). The specific activity was 0.83-0.93 Ci/micromol and the radiochemical purity was 97%. The initial uptake of [11C]MK-912 in mouse brain, heart, lung, liver and kidney was high (5%, 4%, 5%, 17% and 8% per gram of organ, respectively, at 5 min postinjection) and the activities were then slowly cleared from these organs. The uptake of [11C]MK-912 in rat olfactory tubercle, a brain region with high density of alpha2-adrenergi...Continue Reading

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Citations

Apr 30, 2015·Psychopharmacology·Sjoerd J FinnemaSarah Grimwood
Jan 10, 2016·Applied Radiation and Isotopes : Including Data, Instrumentation and Methods for Use in Agriculture, Industry and Medicine·Cheng-Yi ChengChyng-Yann Shiue
Mar 7, 2006·Bioorganic & Medicinal Chemistry·M Van der MeyJ E Leysen
Nov 3, 2004·CNS Spectrums·J McConathyM M Goodman
Feb 3, 2019·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Anna KrzyczmonikOlof Solin
Sep 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Santosh Reddy AlluriKun-Eek Kil
Oct 31, 2020·Frontiers in Neuroscience·Michael KelbermanDavid Weinshenker

Related Concepts

L-657,743-002W
Adrenergic alpha-Antagonists
Brain
Carbon Radioisotopes
Ligands
Macaca mulatta
Quinolizines
Drug or Chemical Tissue Distribution
Tomography, Emission-Computed
Rats, Holtzman

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