Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist.
In 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.
['Rotstein|Benjamin H|BH|', 'Liang|Steven H|SH|', 'Belov|Vasily V|VV|', 'Livni|Eli|E|', 'Levine|Dylan B|DB|', 'Bonab|Ali A|AA|', 'Papisov|Mikhail I|MI|', 'Perlis|Roy H|RH|', 'Vasdev|Neil|N|']
D000818:Animals D001921:Brain D002121:Calcium Channel Blockers D015220:Calcium Channels D002250:Carbon Radioisotopes D004126:Dimethylformamide D004353:Drug Evaluation, Preclinical D006207:Half-Life D006847:Hydrocarbons, Iodinated D007553:Isotope Labeling D017275:Isradipine D008297:Male D059906:Neuroimaging D010539:Permeability D049268:Positron-Emission Tomography D000644:Quaternary Ammonium Compounds D019275:Radiopharmaceuticals D051381:Rats D017207:Rats, Sprague-Dawley
radiosynthesis neuroimaging positron emission tomography carbon-11 isradipine calcium channel blocker