Author: Nakatani, Yuka ; Doi, Hisashi ; Nomura, Yukihiro ; Akimoto, Kouji ; Wada, Yasuhiro ; Mawatari, Aya ; Watanabe, Yasuyoshi ; Kitayoshi, Takahito ; Hayashinaka, Emi ; Nozaki, Satoshi ; Ninomiya, Shinji

PURPOSEThiamine is an essential component of glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is better absorbed than readily-available water-soluble thiamine salts because it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions have not yet been clarified. C-11-labeled thiamine and TTFD were recently synthesized by our group. In this study, to clarify the differences in pharmacokinetics and metabolism of these probes, a quantitative PET imaging study and radiometabolite analysis of C-11-labeled thiamine and TTFD were performed in the rat heart.PROCEDURESPositron emission tomography (PET) imaging with [¹¹C]thiamine and [¹¹C]TTFD was performed in normal rats to determine the pharmacokinetics of these probes, and the radiometabolites of both probes from the blood and heart tissue were analyzed by thin-layer chromatography.RESULTSAccumulation of [¹¹C]TTFD was significantly higher than that of [¹¹C]thiamine in the rat heart. Moreover, as a result of the radiometabolite analysis of heart tissue at 15 min after the injection of [¹¹C]TTFD, thiamine pyrophosphate, which serves as a cofactor for the enzymes involved in glucose metabolism, was found as the major radiometabolite and at a significantly higher level than in the [¹¹C]thiamine-injected group.CONCLUSIONSPET imaging techniques for visualizing the kinetics and metabolism of thiamine using [¹¹C]thiamine and [¹¹C]TTFD were developed in this study. Consequently, noninvasive PET imaging for the pathophysiology of thiamine-related cardiac function may provide novel information about heart failure and related disorders.

01 May 2014·Journal of Nuclear MedicineQ1 · MEDICINE

¹¹C-Cetrozole: An Improved C-¹¹C-Methylated PET Probe for Aromatase Imaging in the Brain

Q1 · MEDICINE

Article

Author: Masaaki Suzuki ; Yumiko Watanabe ; Xiao-Le Li ; Toshiyuki Hiramatsu ; Yasuhiro Wada ; Takamitsu Hosoya ; Kayo Takahashi ; Hisashi Doi ; Yasuyoshi Watanabe ; Tadayuki Takashima ; Hirotaka Onoe ; Kayo Onoe ; Hiroko Nagata

Aromatase (an enzyme that converts androgens to estrogens) in the brain is involved in neuroprotection, synaptic plasticity, and regulation of sexual and emotional behaviors. To investigate the physiologic and pathologic importance of aromatase in the brain, including in humans, we here report the development of a novel PET probe for aromatase, (11)C-cetrozole, which allows noninvasive quantification of aromatase expression.METHODS(11)C-cetrozole was synthesized by the C-(11)C-methylation method developed by our group. In vitro autoradiography of frozen sections and a binding study with rat brain homogenates were conducted to demonstrate the specific binding and the dissociation constant. PET studies with anesthetized rhesus monkeys were performed to analyze the dynamics in the brain.RESULTSIn vitro and in vivo studies using (11)C-cetrozole showed its superiority in brain aromatase imaging in terms of specificity and selectivity, compared with previously developed (11)C-vorozole. PET studies showed that (11)C-cetrozole had a higher signal-to-noise ratio, providing a sharper image than (11)C-vorozole, because the radioactive metabolite of (11)C-vorozole was taken up into the brain. High specific binding of (11)C-cetrozole was observed in the amygdala and hypothalamus, and we also noted binding in the nucleus accumbens of rhesus monkeys for the first time.CONCLUSIONThese results suggest that PET imaging with newly developed (11)C-cetrozole is suitable for quantifying the expression of brain aromatase in vivo, possibly providing critical information regarding the functional roles of aromatase in human neurologic and emotional disorders.

12 Apr 2011·Journal of Pharmacy and PharmacologyQ3 · MEDICINE

Permeability of the blood-brain barrier for atenolol studied by positron emission tomography

Q3 · MEDICINE

Article

Author: Agon, Philippe ; Kaufman, Jean-Marc ; Van Haver, Dirk ; Goethals, Patrick

AbstractThe permeability of the blood-brain barrier for atenolol, a hydrophilic β-adrenergic blocking agent, has been assessed in dogs, by studying the distribution of [11C]atenolol in brain tissue with positron emission tomography. The passage of atenolol into the brain was very limited, but a measurable small net influx into the brain tissues did occur. Osmotic opening of the blood-brain barrier resulted in a marked increase of the atenolol concentrations in brain tissue. The approach described, with sequential non-invasive measurements in brain tissue, is applicable to pharmacokinetic studies of atenolol in man.

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Indication	Highest Phase	Country/Location	Organization	Date
Diagnostic agents	Phase 1	-	Riken Corp.	-
Neoplasms	Preclinical	JP	Riken Corp.	08 Sep 2012

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