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Evaluation of 5-[18F]Fluoropropylepidepride as a potential pet radioligand for imaging dopamine D2 receptors
- Source :
- Synapse. 15:169-176
- Publication Year :
- 1993
- Publisher :
- Wiley, 1993.
-
Abstract
- This study evaluated the utility of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5-(3-[18F]fluoropropyl)-2,3-dimethoxybenzamide ([18F]fluoropropylepidepride), [18F]5-FPrEpid, as a ligar d for PET studies of cerebral dopamine D2 receptors. The in vitro affinity for the rat striatal dopamine D2 receptor, KD 138 pM, was determined by Scatchard analysis of in vitro binding to rat striatal homogenate. The apparent lipophilicity, log kw 1.6, was measured with reverse phase HPLC at pH 7.5. The receptor specificity was determined by competitive displacement of [18F]5-FPrEpid by a variety of neurotransmitter ligands. Only dopamine D2 ligands displaced [18F]5-FPrEpid with high affinity. Positron tomographic imaging studies in primates of [18F]5-FPrEpid demonstrated a stable striatal uptake. of 0.02% injected dose/ml for up to 5 h after injection. The striatal: cerebellar ratio increased from 2 at 15 min, to 7 at 200 min, and to 10 at 300 min. Striatal uptake was displaceable by haloperidol (1 mg/kg) or raclopride (2.5 mg/kg) to cerebellar levels with a t1/2 of washout of 9 or 15 min. Striatal uptake was mildly susceptible to displacement by d-amphetamine (1–2 mg/kg) released endogenous dopamine; d-amphetamine administration produced a 10%/h increase in the rate of striatal washout. Although uptake in the striatum is reversible, an equilibrium between receptor bound [18F]5-FPrEpid in striatum and [18F]5-FPrEpid in plasma is not reached within 5 h postinjection. © 1993 Wiley-Liss. Inc.
- Subjects :
- Male
Fluorine Radioisotopes
medicine.medical_specialty
Pyrrolidines
Prefrontal Cortex
Striatum
Binding, Competitive
Hippocampus
Iodine Radioisotopes
Rats, Sprague-Dawley
Radioligand Assay
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Dopamine receptor D2
Internal medicine
Haloperidol
medicine
Radioligand
Animals
Receptor
Neurotransmitter
Cerebral Cortex
Raclopride
Receptors, Dopamine D2
Brain
Macaca mulatta
Rats
Kinetics
Endocrinology
Biochemistry
chemistry
Benzamides
Lipophilicity
Tomography, Emission-Computed
medicine.drug
Subjects
Details
- ISSN :
- 10982396 and 08874476
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- Synapse
- Accession number :
- edsair.doi.dedup.....0385483675e71719a5996573363c4e10