In vivo labeling of cocaine receptors with sup 3 H-(-) cocaine, sup 3 H-WIN 35,065-2 and sup 3 H-WIN 35,428

Conference · Mon Feb 26 00:00:00 EST 1990 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5533309

Scheffel, U; Boja, J W; Stathis, M; Kuhar, M J ^[1]

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1. Johns Hopkins Medical Institutions, Baltimore, MD (United States)

{sup 11}C-(-)cocaine (-COC) has recently been employed to image -COC binding sites in vivo using PET. Two analogs of -COC, WIN 35,065-2 (WIN-2) and WIN 35,428 (CFT), have been shown in vitro to exhibit higher affinity for the -COC receptor than -COC. The present study evaluates {sup 3}H-WIN-2 and {sup 3}H-CFT as in vivo receptor labels in mice with a view towards the use of these compounds as PET ligands for -COC receptors in the living human brain. {sup 3}H-labeled -COC, WIN-2 and CFT were injected i.v. into mice and their specific binding in the CNS determined. Peak striatal/cerebellar (S/C) ratios were reached at 5 minutes post injection with -COC (1.56), at 45 minutes with {sup 3}H-WIN-2 (3.30) and 60 minutes with {sup 3}H-CFT (4.0). The specificity of in vivo binding of {sup 3}H-WIN-2 and {sup 3}H-CFT was tested by pre-injection of various drugs. Binding of {sup 3}H-WIN-2 and {sup 3}H-CFT was dose-dependently blocked by cold WIN-2 and CFT, and by dopamine uptake site inhibitors (mazindol, GBR 12,909, nomifensine), but not by (+)COC, paroxetine and desipramine. The data indicate that {sup 3}H-WIN-2 and {sup 3}H-CFT exhibit improved in vivo binding (higher S/C ratios, longer retention time at the -COC receptor/dopamine transporter) compared to -COC and support their testing in PET studies.

• OSTI ID: 5533309
• Report Number(s): CONF-9004153-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 4:3; Conference: 74. annual meeting of the Federation of American Societies for Experimental Biology, Washington, DC (United States), 1-5 Apr 1990; ISSN 0892-6638
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
RECEPTORS
LABELLING
BIOCHEMICAL REACTION KINETICS
CARBON 11
CENTRAL NERVOUS SYSTEM
COCAINE
COMPARATIVE EVALUATIONS
DOPAMINE
DRUGS
IN VIVO
LIGANDS
MICE
POSITRON COMPUTED TOMOGRAPHY
RETENTION
TRITIUM COMPOUNDS
ALKALOIDS
AMINES
ANESTHETICS
ANIMALS
ANTIDEPRESSANTS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BETA-PLUS DECAY RADIOISOTOPES
CARBON ISOTOPES
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM AGENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
COMPUTERIZED TOMOGRAPHY
DIAGNOSTIC TECHNIQUES
EMISSION COMPUTED TOMOGRAPHY
EVALUATION
EVEN-ODD NUCLEI
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
ISOTOPES
KINETICS
LIGHT NUCLEI
MAMMALS
MEMBRANE PROTEINS
MINUTES LIVING RADIOISOTOPES
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ORGANIC COMPOUNDS
PHENOLS
POLYPHENOLS
PROTEINS
PSYCHOTROPIC DRUGS
RADIOISOTOPES
REACTION KINETICS
RODENTS
SYMPATHOMIMETICS
TOMOGRAPHY
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics