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

Conference · Wed Jun 01 00:00:00 EDT 1994

OSTI ID:10158915

McPherson, D W; Luo, H; Knapp, Jr, F F

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 A brominated analogue, ``BrQNP,`` in which the iodine has been replaced by a bromine atom, has also been prepared and was shown to block the in vivo uptake of IQNP in the brain and heart and therefore has potential for positron emission tomographic (PET) studies of m-AChR.

• Research Organization: Oak Ridge National Lab., TN (United States)
• Sponsoring Organization: USDOE, Washington, DC (United States)
• DOE Contract Number: AC05-84OR21400
• OSTI ID: 10158915
• Report Number(s): CONF-940301-36; ON: DE94013261
• 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]
• Country of Publication: United States
• Language: English

Related Subjects

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