Nuclear medicine program progress report for quarter ending June 30, 1994

Technical Report · Mon Aug 01 00:00:00 EDT 1994

DOI:https://doi.org/10.2172/10177586· OSTI ID:10177586

Knapp, Jr, F F; Ambrose, K R; Beets, A L; Lambert, C R; McPherson, D W; Mirzadeh, S; Luo, H

In this report we describe tile first successful synthesis and in vivo evaluation of a fluorinated analogue of the IQNP muscarinic-cholinergic receptor ligand. Unanticipated synthetic hurdles lead to several unsuccessful approaches before the synthesis of a model compound was achieved. The successful route involved introduction of the fluoroethyl moiety at an early stage of the synthesis by alkylation of ethyl 1,3-dithiane-2-carboxylate with 1-fluoro-2-bromoethane. Subsequent unmasking of the carbonyl, followed by introduction of the phenyl group with phenylmagnesium bromide and subsequent transesterification with racemic quinuclidinol afforded the target compound, 1-azabicyclo[2.2.2]oct-3-yl {alpha}-(1-fluoroethan-2-yl)-{alpha}-hydroxy-{alpha}-phenylacetate (QNF). Pretreatment of Fisher rats with QNF one hour prior to the intravenous administration of the [I-131]-Z-(R,R) IQNP isomer demonstrated that the new fluoro analogue blocked uptake of iodine-131 in those regions of the brain rich in muscarinic-cholinergic receptors measured three hours after injection. As an example, the control values for group of nontreated animals were (5 animals; mean {+-} SD): cortex, 1.20{+-}0.27; striatum, 0.73{+-}0.19; pons, 0.70{+-}0.20; cerebellum, 0.43{+-}0.114. Brains from animals pretreated with the fluoro analogue had the following values (mean{+-}SD; % decrease): cortex, 0.67{+-}0.15 (65%); striatum, 0.35{+-}0.114 (52%); pons, 0.40{+-}0.08 (43%); cerebellum, 0.16{+-}0.09(63%). Also during this period several tungsten-188/rhenium-188 generators and tin-117m samples were provided for collaborative studies.

• Research Organization: Oak Ridge National Lab., TN (United States)
• Sponsoring Organization: USDOE, Washington, DC (United States)
• DOE Contract Number: AC05-84OR21400
• OSTI ID: 10177586
• Report Number(s): ORNL/TM--12789; ON: DE94017530
• Country of Publication: United States
• Language: English

Related Subjects

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
400703
550604
62 RADIOLOGY AND NUCLEAR MEDICINE
BIOLOGICAL LOCALIZATION
BRAIN
CHEMICAL PREPARATION
FLUORINE 18
IODINE 131
NUCLEAR MEDICINE
POSITRON COMPUTED TOMOGRAPHY
PROGRESS REPORT
RADIOISOTOPE PRODUCTION
RADIOISOTOPES
RATS
RECEPTORS
TRACER TECHNIQUES
UNSEALED RADIONUCLIDES IN THERAPY
UPTAKE