Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist

Benjamin H. Rotstein; Steven H. Liang; Vasily V. Belov; Eli Livni; Dylan B. Levine; Ali A. Bonab; Mikhail I. Papisov; Roy H. Perlis; Neil Vasdev

doi:10.3390/molecules20069550

Molecules (May 2015)

Practical Radiosynthesis and Preclinical Neuroimaging of [11C]isradipine, a Calcium Channel Antagonist

Benjamin H. Rotstein,
Steven H. Liang,
Vasily V. Belov,
Eli Livni,
Dylan B. Levine,
Ali A. Bonab,
Mikhail I. Papisov,
Roy H. Perlis,
Neil Vasdev

Affiliations

Benjamin H. Rotstein: 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
Steven H. Liang: 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
Vasily V. Belov: 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
Eli Livni: 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
Dylan B. Levine: 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
Ali A. Bonab: 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
Mikhail I. Papisov: 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
Roy H. Perlis: Department of Psychiatry and Center for Experimental Drugs and Diagnostics, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA
Neil Vasdev: 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

DOI: https://doi.org/10.3390/molecules20069550
Journal volume & issue: Vol. 20, no. 6
pp. 9550 – 9559

Abstract

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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.

Published in Molecules

ISSN: 1420-3049 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Science: Chemistry: Organic chemistry
Website: http://www.mdpi.com/journal/molecules

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