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.
The blood-brain barrier permeability of ginkgolide B was examined using positron emission tomography (PET) probes of a18F-incorporated ginkgolide B ([18F]-2) and a11C-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.
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.
Hisashi
H
Doi
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.
Kengo
K
Sato
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.
Hideo
H
Shindou
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.
Kengo
K
Sumi
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.
Hiroko
H
Koyama
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.
Takamitsu
T
Hosoya
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.
Yasuyoshi
Y
Watanabe
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.
Satoshi
S
Ishii
PET Center, Central Research Laboratory, Hamamatsu Photonics K.K., 5000 Hirakuchi, Hamakita-ku, Hamamatsu 434-8601, Japan. Electronic address: tsukada@crl.hpk.co.jp.
Hideo
H
Tsukada
Department of Chemistry, Columbia University, 3000 Broadway, New York, NY 10027, USA. Electronic address: kn5@columbia.edu.
Koji
K
Nakanishi
Department of Clinical and Experimental Neuroimaging, National Center for Geriatrics and Gerontology, Obu, Aichi 474-8511, Japan. Electronic address: suzukims@ncgg.go.jp.
Masaaki
M
Suzuki
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D046934:Ginkgolides / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D000882:Haplorhini; D007783:Lactones / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D015394:Molecular Structure; D010539:Permeability / Q000187:drug effects; D049268:Positron-Emission Tomography; D051381:Rats; D013329:Structure-Activity Relationship
D046934:Ginkgolides; D007783:Lactones; C045856:ginkgolide B
Blood–brain barrier; C-[(11)C]methylation; Ginkgolide B; PET; Platelet-activating factor