Rotstein, Benjamin H.Liang, HuanBelov, VasilyLivni, EliLevine, Dylan B.Bonab, Ali A.Papisov, MikhailPerlis, Roy H.Vasdev, Neil2016-06-142016Rotstein, Benjamin H., Steven H. Liang, Vasily V. Belov, Eli Livni, Dylan B. Levine, Ali A. Bonab, Mikhail I. Papisov, Roy H. Perlis, and Neil Vasdev. 2016. “Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, A Calcium Channel Antagonist.” Molecules (Basel, Switzerland) 20 (6): 9550-9559. doi:10.3390/molecules20069550. http://dx.doi.org/10.3390/molecules20069550.1420-3049http://nrs.harvard.edu/urn-3:HUL.InstRepos:27320378In 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.en-UScarbon-11radiosynthesisisradipinepositron emission tomographyneuroimagingcalcium channel blockerJournal Article2016-06-1410.3390/molecules20069550