[11C]metaraminol, a false neurotransmitter: preparation, metabolite studies and positron emission tomography examination in monkey.
No-carrier-added racemic [11C]metaraminol was prepared by a selective condensation of [11C]nitroethane with 3-hydroxy-benzaldehyde using tetrabutylammonium fluoride in tetrahydrofuran (THF) as a catalyst, followed by a reduction with Raney nickel in formic acid. [11C]Metaraminol was produced in 30 to 45% decay-corrected yield from [11C]nitroethane (13 to 20% decay corrected from [11C]CO2) within 45 to 55 min total synthesis time. Reversed phase high-performance liquid chromatography (HPLC) was used for the separation of the racemic erythro- and threo-forms of [11C]metaraminol. The radiochemical purity was higher than 98%, and the specific radioactivity at the end of synthesis was 500 to 800 Ci/mmol (18 to 30 GBq/mumol). Positron emission tomography (PET) examination of racemic erythro-[11C]metaraminol in a Cynomolgus monkey showed a high uptake of radioactivity in the heart. Following pretreatment with the selective norepinephrine reuptake inhibitor desipramine, the radioactivity uptake in the myocardium was markedly reduced (80%), demonstrating the specificity of erythro-[11C]metaraminol for the norepinephrine reuptake system of the heart. Pretreatment with desipramine had no effect on radioactivity in lung. The metabolism was rapid for [11C]metaraminol. The amounts of the total radioactivity representing [11C]metaraminol in plasma, determined by HPLC, were 14% at 6 min and 8% at 34 min. The high specific uptake of racemic erythro-[11C]metaraminol indicates that enantiomerically pure (R,S)-[11C]metaraminol has potential for detailed mapping of the sympathetic innervation of the human myocardium.
Någren
K
K
Turku University Cyclotron-pet Center, Radiopharmaceutical Chemistry Laboratory, Finland.
Halldin
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C
Swahn
C G
CG
Suhara
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T
Farde
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D000818:Animals; D002245:Carbon Dioxide; D002250:Carbon Radioisotopes; D003891:Desipramine / Q000494:pharmacology; D004980:Ethane / Q000031:analogs & derivatives; D006321:Heart / Q000000981:diagnostic imaging / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007536:Isomerism; D007553:Isotope Labeling / Q000379:methods; D008252:Macaca fascicularis; D008297:Male; D008680:Metaraminol / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D009206:Myocardium / Q000378:metabolism*; D009595:Nitroparaffins; D009638:Norepinephrine / Q000494:pharmacology; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*
D002250:Carbon Radioisotopes; D007202:Indicators and Reagents; D009595:Nitroparaffins; D002245:Carbon Dioxide; C014705:nitroethane; D008680:Metaraminol; D004980:Ethane; D003891:Desipramine; D009638:Norepinephrine