Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist
AbstractIn the interest of developing in vivo positron emission tomography (PET) probes for neuroimaging of calcium channels, we have prepared a carbon-11 isotopologue of a dihydropyridine Ca2+-channel antagonist, isradipine. Desmethyl isradipine (4-(benzo[c][1,2,5]oxadiazol-4-yl)-5-(isopropoxycarbonyl)-2,6-dimethyl-1,4-dihydropyridine -3-carboxylic acid) was reacted with [11C]CH3I in the presence of tetrabutylammonium hydroxide in DMF in an HPLC injector loop to produce the radiotracer in a good yield (6 ± 3% uncorrected radiochemical yield) and high specific activity (143 ± 90 GBq·µmol−1 at end-of-synthesis). PET imaging of normal rats revealed rapid brain uptake at baseline (0.37 ± 0.08% ID/cc (percent of injected dose per cubic centimeter) at peak, 15–60 s), which was followed by fast washout. After pretreatment with isradipine (2 mg·kg−1, i.p.), whole brain radioactivity uptake was diminished by 25%–40%. This preliminary study confirms that [11C]isradipine can be synthesized routinely for research studies and is brain penetrating. Further work on Ca2+-channel radiotracer development is planned. View Full-Text
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Rotstein, B.H.; Liang, S.H.; Belov, V.V.; Livni, E.; Levine, D.B.; Bonab, A.A.; Papisov, M.I.; Perlis, R.H.; Vasdev, N. Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist. Molecules 2015, 20, 9550-9559.
Rotstein BH, Liang SH, Belov VV, Livni E, Levine DB, Bonab AA, Papisov MI, Perlis RH, Vasdev N. Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist. Molecules. 2015; 20(6):9550-9559.Chicago/Turabian Style
Rotstein, Benjamin H.; Liang, Steven H.; Belov, Vasily V.; Livni, Eli; Levine, Dylan B.; Bonab, Ali A.; Papisov, Mikhail I.; Perlis, Roy H.; Vasdev, Neil. 2015. "Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist." Molecules 20, no. 6: 9550-9559.