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Title: Development of radiohalogenated muscarinic ligands for the in vivo imaging of m-AChR by nuclear medicine techniques

Alterations in the density of acetylcholinergic muscarinic receptors (m-AChR) have been observed in various dementias. This has spurred interest in the development of radiohalogenated ligands which can be used for the non-invasive in vivo detection of m-AChR by nuclear medicine techniques. We have developed a new ligand 1-azabicyclo[2.2.2]oct-3-yl ({alpha}-hydroxy-{alpha}-(1-iodo-1-propen-3-yl)-{alpha}-phenylacetate (IQNP,12) which demonstrates high affinity for the muscarinic receptor. When labeled with radioiodine it has been shown to be selective and specific for m-ACHR. Initial studies on the separation and in vivo evaluation of the various isomers of IQNP have shown that the stereochemistry of the chiral centers and the configuration around the double bond play an important role in m-AChR subtype specificity. In vivo evaluation of these stereoisomers demonstrate that E-(R,R)-IQNP has a high affinity for the M{sub 1} muscarinic subtype while Z-(R,R)-IQNP demonstrate a high affinity for M{sub 1} and M{sub 2} receptor subtypes. These data demonstrate IQNP (12) has potential for use in the non-evasive in vivo detection of m-AChR by single photon emission computed tomography (SPECT). A brominated analogue, ``BrQNP,`` in which the iodine has been replaced by a bromine atom, has also been prepared and was shown to block the in vivo uptake of IQNP inmore » the brain and heart and therefore has potential for positron emission tomographic (PET) studies of m-AChR.« less
Authors:
; ;
Publication Date:
OSTI Identifier:
10158915
Report Number(s):
CONF-940301--36
ON: DE94013261
DOE Contract Number:
AC05-84OR21400
Resource Type:
Conference
Resource Relation:
Conference: 207. spring national meeting of the American Chemical Society (ACS),San Diego, CA (United States),13-18 Mar 1994; Other Information: PBD: [1994]
Research Org:
Oak Ridge National Lab., TN (United States)
Sponsoring Org:
USDOE, Washington, DC (United States)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; 38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY; PARASYMPATHOMIMETICS; LABELLING; TISSUE DISTRIBUTION; RADIOPHARMACEUTICALS; CHEMICAL PREPARATION; NUCLEAR MEDICINE; PARASYMPATHOLYTICS; IODINE 123; FLUORINE 18; STRUCTURE-ACTIVITY RELATIONSHIPS; RATS; CEREBRAL CORTEX; CEREBRUM; CEREBELLUM; HEART 550601; 400703; UNSEALED RADIONUCLIDES IN DIAGNOSTICS; RADIOISOTOPE PRODUCTION