Improved synthesis of the peripheral benzodiazepine receptor ligand [11C]DPA-713 using [11C]methyl triflate.
Recently, the pyrazolopyrimidine, [11C] N,N-Diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide (DPA-713) has been reported as a new promising marker for the study of peripheral benzodiazepine receptors with positron emission tomography. In the present study, DPA-713 has been labelled from the corresponding nor-analogue using [11C]methyl triflate (CH3OTf). Conditions for HPLC were also modified to include physiological saline (aq. 0.9% NaCl)/ethanol:60/40 as mobile phase making it suitable for injection. The total time of radiosynthesis, including HPLC purification, was 18-20 min. This reported synthesis of [11C]DPA-713, using [11C]CH3OTf, resulted in an improved radiochemical yield (30-38%) compared to [11C]methyl iodide (CH3I) (9) with a simpler purification method. This ultimately enhances the potential of [11C]DPA-713 for further pharmacological and clinical evaluation. These improvements make this radioligand more suitable for automated synthesis which is of benefit where multi-dose preparations and repeated syntheses of radioligand are required.
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Service Hospitalier Frédéric Joliot, Département de Recherche Médicale, CEA/DSV, 4 place du Général Leclerc, F-91401 Orsay, France.
Dollé
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James
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Bramoullé
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Boutin
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Besret
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Grégoire
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Valette
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Bottlaender
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Tavitian
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Hantraye
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Selleri
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Kassiou
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D000081:Acetamides / Q000138:chemical synthesis* / Q000737:chemistry; D002250:Carbon Radioisotopes / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D007553:Isotope Labeling / Q000379:methods; D008024:Ligands; D008698:Mesylates / Q000737:chemistry*; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000737:chemistry; D011963:Receptors, GABA-A / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet
D000081:Acetamides; D002250:Carbon Radioisotopes; D008024:Ligands; D008698:Mesylates; C507091:N,N-diethyl-2-(2-(4-methoxyphenyl)-5,7-dimethyl-pyrazolo(1,5-a)pyrimidin-3-yl)-acetamide; D011720:Pyrazoles; D011743:Pyrimidines; D011963:Receptors, GABA-A; C078465:methyl triflate