title: Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist.
abstract: 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.
authors.affiliation: Department of Radiology, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging and Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. rotstein.benjamin@mgh.harvard.edu.
authors.forename: Benjamin H
authors.initials: BH
authors.lastname: Rotstein
authors.affiliation: Department of Radiology, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging and Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. liang.steven@mgh.harvard.edu.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Liang
authors.affiliation: Department of Radiology, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging and Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. vbelov@mgh.harvard.edu.|Department of Research, Shriners Hospitals for Children-Boston, 51 Blossom Street, Boston, MA 02114, USA. vbelov@mgh.harvard.edu.
authors.forename: Vasily V
authors.initials: VV
authors.lastname: Belov
authors.affiliation: Department of Radiology, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging and Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. elivni@mgh.harvard.edu.
authors.forename: Eli
authors.initials: E
authors.lastname: Livni
authors.affiliation: Department of Radiology, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging and Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. dblevine@mgh.harvard.edu.|Department of Research, Shriners Hospitals for Children-Boston, 51 Blossom Street, Boston, MA 02114, USA. dblevine@mgh.harvard.edu.
authors.forename: Dylan B
authors.initials: DB
authors.lastname: Levine
authors.affiliation: Department of Radiology, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging and Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. bonab@pet.mgh.harvard.edu.|Department of Research, Shriners Hospitals for Children-Boston, 51 Blossom Street, Boston, MA 02114, USA. bonab@pet.mgh.harvard.edu.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Bonab
authors.affiliation: Department of Radiology, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging and Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. papisov@helix.mgh.harvard.edu.|Department of Research, Shriners Hospitals for Children-Boston, 51 Blossom Street, Boston, MA 02114, USA. papisov@helix.mgh.harvard.edu.
authors.forename: Mikhail I
authors.initials: MI
authors.lastname: Papisov
authors.affiliation: Department of Psychiatry and Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA. rperlis@mgh.harvard.edu.
authors.forename: Roy H
authors.initials: RH
authors.lastname: Perlis
authors.affiliation: Department of Radiology, Harvard Medical School, Division of Nuclear Medicine and Molecular Imaging and Center for Advanced Medical Imaging Sciences, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. vasdev.neil@mgh.harvard.edu.
authors.forename: Neil
authors.initials: N
authors.lastname: Vasdev
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D015220:Calcium Channels / Q000378:metabolism; D002250:Carbon Radioisotopes; D004126:Dimethylformamide / Q000737:chemistry; D004353:Drug Evaluation, Preclinical; D006207:Half-Life; D006847:Hydrocarbons, Iodinated / Q000737:chemistry*; D007553:Isotope Labeling / Q000379:methods*; D017275:Isradipine / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D059906:Neuroimaging / Q000379:methods*; D010539:Permeability; D049268:Positron-Emission Tomography; D000644:Quaternary Ammonium Compounds / Q000737:chemistry; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002250:Carbon Radioisotopes; D006847:Hydrocarbons, Iodinated; D000644:Quaternary Ammonium Compounds; D019275:Radiopharmaceuticals; D004126:Dimethylformamide; C009405:tetrabutylammonium; C014055:methyl iodide; D017275:Isradipine
keywords: calcium channel blocker; carbon-11; isradipine; neuroimaging; positron emission tomography; radiosynthesis