Synthesis and biological evaluation of 18F-Norfallypride in the rodent brain using PET imaging
| Autor: | Robert Coleman, Suresh K. Pandey, Neema Pithia, Jogeshwar Mukherjee, Neal Gulati, Ritu Kant |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Cancer Research Pyrrolidines Chemistry Techniques Synthetic Article Rats Sprague-Dawley chemistry.chemical_compound Dopamine receptor D3 In vivo Animals Radiology Nuclear Medicine and imaging Benzamide 5-HT receptor Receptors Dopamine D2 Receptors Dopamine D3 Brain Rats chemistry Biochemistry Fallypride Dopamine receptor Positron-Emission Tomography Benzamides Biophysics Molecular Medicine Serotonin Ex vivo |
| Zdroj: | Nuclear Medicine and Biology. 40:697-704 |
| ISSN: | 0969-8051 |
| Popis: | Norfallypride ( N -[(2-pyrolidinyl)methyl]-2,3-dimethoxy-5-(3'-fluoropropyl)benzamide), an analog of fallypride, has been synthesized and evaluated as a potential PET imaging agent for dopamine receptors with increased subtype selectivity. In order to synthesize 18 F-Norfallypride, the substituted benzamide tosylate ( S )- N -[(1-BOC-2-pyrolidinyl)methyl]-2,3-dimethoxy-5-(3'-tosyloxypropyl)-benzamide) was radiolabeled with 18 F using Kryptofix and K 2 CO 3 in acetonitrile and deprotected with trifluoroacetic acid to yield ( S )- 18 F-Norfallypride in approx. 10% radiochemical yields. Norfallypride exhibited an IC 50 of 0.63μM for displacing 18 F-fallypride in rat brain slices. In vitro rat brain autoradiographic studies revealed weak binding of 18 F-norfallypride to striatal regions. PET imaging in rats showed low brain uptake of 18 F-norfallypride in the rat brain. Ex vivo brain PET analysis displayed binding of 18 F-norfallypride in several brain regions. With respect to the cerebellum, ex vivo PET ratios were: striatum>3; hypothalamus>2; hippocampus~2; cerebellar nuclei >2 while autoradiographic ratios were 14, 9, 4 and 6 respectively. 18 F-Norfallypride exhibited a unique binding profile to rat brain regions known to contain significant amounts of dopamine D3 and serotonin 5HT 3 receptors. Efforts are currently under way to increase brain permeability and fully characterize the binding of 18 F-norfallypride in vivo. |
| Databáze: | OpenAIRE |
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