PET measurement of FK506 concentration in a monkey model of stroke.

PET measurement of FK506 concentration in a monkey model of stroke. Research Abstract Details 

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PET measurement of FK506 concentration in a monkey model of stroke. Abstract Text:

Yoshihiro Murakami,Hiroyuki Takamatsu,Akihiro Noda,Kazuhiko Osoda,Shintaro Nishimura,

INTRODUCTION: The immunosuppressive agent FK506 (tacrolimus) has neuroprotective properties in an experimental model of cerebral ischemia. To improve the accuracy of clinical studies in acute stroke, a clinical dose setting should be based on the brain concentration, but not on the blood concentration of agents in humans. We have already established a measurement method using PET for FK506 concentration in the normal monkey brain, which could be applicable for human study; however, under ischemic conditions, in this study, we aimed to examine the brain concentration of FK506 in a monkey model of stroke. METHODS: Studies were performed on six male cynomolgus monkeys (Macaca fascicularis) and a middle cerebral artery (MCA) occlusion model was used. Regional cerebral blood flow (rCBF) was measured by an intravenous injection of [(15)O]H(2)O 165 min after MCA occlusion. FK506 (0.1 mg/kg) containing [(11)C]FK506 was intravenously injected into the monkeys 180 min after MCA occlusion, and dynamic PET images were acquired for 30 min after administration. FK506 concentrations in the brain were calculated in moles per liter (M) units using the specific activity of injected FK506. RESULTS: MCA occlusion produced ischemia, confirmed by rCBF measurement before the administration of [(11)C]FK506. Fifteen minutes after FK506 (0.1 mg/kg) administration, the concentrations in the contralateral and ipsilateral cortex were 22.4+/-6.4 and 19.7+/-4.0 ng/g, respectively. CONCLUSION: We successfully measured the brain concentration of FK506 in a monkey model of stroke. The difference between the contralateral and ipsilateral concentrations of FK506 was not significant. This characteristic that FK506 readily penetrates ischemic tissue as well as normal tissue might explain the neuroprotective effect of FK506 in the ischemic brain and is suitable for the treatment of stroke patients.

PET measurement of FK506 concentration in a monkey model of stroke. Publishing Authors By Initials

Y Murakami,H Takamatsu,A Noda,K Osoda,S Nishimura,

For similar organic chemicals: lactones: macrolides: tacrolimus research abstracts see: organic chemicals: lactones: macrolides: tacrolimus research

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PET measurement of FK506 concentration in a monkey model of stroke. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Nuclear medicine and biology

VOLUME: 34

Page Numbers: 703-7

Journal Abbreviation: Nucl. Med. Biol.

ISSN: 0969-8051

DAY: 21

MONTH: Aug

YEAR: 2007

PET measurement of FK506 concentration in a monkey model of stroke. Information

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LANGUAGE: eng

NlmUniqueID: 9304420

PET measurement of FK506 concentration in a monkey model of stroke. Keywords Mesh Terms:

KEYWORDS: Tacrolimus

MESH TERMS: pharmacokinetics

Chemical & Substance for Abstract: PET measurement of FK506 concentration in a monkey model of stroke. Information

Substance Name: Tacrolimus

Registry Number: 109581-93-3

Grant and Affiliation Information for PET measurement of FK506 concentration in a monkey model of stroke.

AFFILIATION: The Medical and Pharmacological Research Center Foundation, Hakui City, Ishikawa 925-0613, Japan. murakami@mprcf.or.jp

Country: England

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MEDLINETA: Nucl Med Biol

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