Synthesis and evaluation of (/sup 125/I)iodothienoperidol as a potential receptor site directed brain imaging agent
This study was undertaken to design and evaluate radioligands for the noninvasive quantification of dopamine receptors in the brain. The approach involved the preparation of the iodothienyl analog I of haloperidol II, a well characterized dopamine antagonist which has been labeled with F-18 and C-11. The synthesis involved the addition of 5-trimethylstannyl-2-thienyllithium so the piperidone intermediate. The product was characterized by spectroscopic and analytic methods and radioiodinated via electrophilic iododestannylation to yield the product in 75-85% isolated yield. The tissue distribution of the radiochemical was evaluated in rats as a function of time, 0.25-2 hrs, and in the presence or absence of haloperidol (1 mg/kg) to measure receptor binding. The results indicated that the 0.25 h uptake in the brain was high (2.2% ID) and that the washout of the activity was relatively slow, 1.3% ID present at 2 hr. The Br/B1 values remained relatively constant over that time interval (9.3-12.1:1). Coadministration of 1 mg/kg haloperidol markedly reduced the uptake in the brain at 0.25 and 2 hr (55% and 62%) with much less of an effect on the nontarget tissues. The study indicates that the authors have prepared a radiotracer, labeled with iodine, that demonstrates both good brain uptake and selectivity as well as a specific binding site component.
- Research Organization:
- College of Pharmacy, Northeastern Univ. and Dept. of Radiology, The Childrens Hospital, Boston, MA 02115
- OSTI ID:
- 7030650
- Report Number(s):
- CONF-850611-; TRN: 87-010788
- Journal Information:
- J. Nucl. Med.; (United States), Vol. 26:5; Conference: 32. annual meeting of the Society of Nuclear Medicine, Houston, TX, USA, 2 Jun 1985
- Country of Publication:
- United States
- Language:
- English
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38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEAR CHEMISTRY
CENTRAL NERVOUS SYSTEM AGENTS
CHEMICAL PREPARATION
TISSUE DISTRIBUTION
UPTAKE
DOPAMINE
IODINATION
LABELLING
RECEPTORS
IODINE 125
RADIOCHEMISTRY
LITHIUM COMPOUNDS
BINDING ENERGY
BRAIN
CHEMICAL BONDS
EVALUATION
LIGANDS
RATS
REACTION INTERMEDIATES
REDUCTION
SPECTROSCOPY
SYMPATHOLYTICS
TIME DEPENDENCE
TRACER TECHNIQUES
WASHOUT
ALKALI METAL COMPOUNDS
AMINES
ANIMALS
AROMATICS
AUTONOMIC NERVOUS SYSTEM AGENTS
BETA DECAY RADIOISOTOPES
BODY
CARDIOTONICS
CARDIOVASCULAR AGENTS
CENTRAL NERVOUS SYSTEM
CHEMICAL REACTIONS
CHEMISTRY
DAYS LIVING RADIOISOTOPES
DISTRIBUTION
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
ENERGY
HALOGENATION
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
MAMMALS
MEMBRANE PROTEINS
NERVOUS SYSTEM
NEUROREGULATORS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PHENOLS
POLYPHENOLS
PRECIPITATION SCAVENGING
PROTEINS
RADIOISOTOPES
RODENTS
SEPARATION PROCESSES
SYMPATHOMIMETICS
SYNTHESIS
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics
400700 - Radiochemistry & Nuclear Chemistry