Blood-brain barrier permeability of ginkgolide: Comparison of the behavior of PET probes 7α-[18F]fluoro- and 10-O-p-[11C]methylbenzyl ginkgolide B in monkey and rat brains

Hisashi Doi; Kengo Sato; Hideo Shindou; Kengo Sumi; Hiroko Koyama; Takamitsu Hosoya; Yasuyoshi Watanabe; Satoshi Ishii; Hideo Tsukada; Koji Nakanishi; Masaaki Suzuki

doi:10.1016/j.bmc.2016.08.032

Blood-brain barrier permeability of ginkgolide: Comparison of the behavior of PET probes 7α-[¹⁸F]fluoro- and 10-O-p-[¹¹C]methylbenzyl ginkgolide B in monkey and rat brains

Bioorg Med Chem. 2016 Nov 1;24(21):5148-5157. doi: 10.1016/j.bmc.2016.08.032. Epub 2016 Aug 23.

Authors

Hisashi Doi¹, Kengo Sato², Hideo Shindou³, Kengo Sumi⁴, Hiroko Koyama⁵, Takamitsu Hosoya⁶, Yasuyoshi Watanabe⁷, Satoshi Ishii⁸, Hideo Tsukada⁹, Koji Nakanishi¹⁰, Masaaki Suzuki¹¹

Affiliations

¹ Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: hisashi.doi@riken.jp.
² PET Medical Application Group, Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita-ku, Hamamatsu 434-8601, Japan. Electronic address: satoken@crl.hpk.co.jp.
³ Department of Lipid Signaling, Research Institute, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan. Electronic address: hshindou-tky@umin.net.
⁴ Division of Regeneration and Advanced Medical Science, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. Electronic address: kesumi@dwti.co.jp.
⁵ Division of Regeneration and Advanced Medical Science, Graduate School of Medicine, Gifu University, 1-1 Yanagido, Gifu 501-1194, Japan. Electronic address: hirokok@gifu-u.ac.jp.
⁶ Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062, Japan. Electronic address: thosoya.cb@tmd.ac.jp.
⁷ Division of Bio-Function Dynamics Imaging, RIKEN Center for Life Science Technologies (CLST), 6-7-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan. Electronic address: yywata@riken.jp.
⁸ Department of Immunology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan. Electronic address: satishii@med.akita-u.ac.jp.
⁹ PET Center, Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita-ku, Hamamatsu 434-8601, Japan. Electronic address: tsukada@crl.hpk.co.jp.
¹⁰ Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, USA. Electronic address: kn5@columbia.edu.
¹¹ Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan. Electronic address: suzukims@ncgg.go.jp.

PMID: 27614918
DOI: 10.1016/j.bmc.2016.08.032

Abstract

The blood-brain barrier permeability of ginkgolide B was examined using positron emission tomography (PET) probes of a ¹⁸F-incorporated ginkgolide B ([¹⁸F]-2) and a ¹¹C-incorporated methylbenzyl-substituted ginkgolide B ([¹¹C]-3). PET studies in monkeys showed low uptake of [¹⁸F]-2 into the brain, but small amounts of [¹¹C]-3 were accumulated in the parenchyma. Furthermore, when cyclosporine A was preadministered to rats, the accumulation of [¹⁸F]-2 in the rat brain did not significantly change, however, the accumulation of [¹¹C]-3 was five times higher than that in the control rat. These results provide effective approaches for investigating the drug potential of ginkgolides.

Keywords: Blood–brain barrier; C-[(11)C]methylation; Ginkgolide B; PET; Platelet-activating factor.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood-Brain Barrier / drug effects
Blood-Brain Barrier / metabolism*
Brain / drug effects
Brain / metabolism*
Dose-Response Relationship, Drug
Ginkgolides / chemical synthesis
Ginkgolides / chemistry
Ginkgolides / pharmacokinetics*
Ginkgolides / pharmacology
Haplorhini
Lactones / chemical synthesis
Lactones / chemistry
Lactones / pharmacokinetics*
Lactones / pharmacology
Molecular Structure
Permeability / drug effects
Positron-Emission Tomography*
Rats
Structure-Activity Relationship

Substances

Ginkgolides
Lactones
ginkgolide B