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Meeting ReportMolecular Targeting Probes - Radioactive and Nonradioactive

Pharmacokinetics of [18F]mefway, a probe for brain serotonin 1A receptor imaging, in rats

Byoung Soo Kim, Jae Yong Choi, Eun Jung Kim, Dan Bee Choi, Chi Hoon Yi, Sang Jin Han, Young Hoon Ryu and Tae Hyun Choi
Journal of Nuclear Medicine May 2013, 54 (supplement 2) 1106;
Byoung Soo Kim
1Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
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Jae Yong Choi
2Nuclear Medicine, Kangnam Severance Hospital, Seoul, Republic of Korea
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Eun Jung Kim
1Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
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Dan Bee Choi
1Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
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Chi Hoon Yi
1Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
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Sang Jin Han
1Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
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Young Hoon Ryu
2Nuclear Medicine, Kangnam Severance Hospital, Seoul, Republic of Korea
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Tae Hyun Choi
1Molecular Imaging, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
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Abstract

1106

Objectives [18F]Mefway has been developed for imaging the serotonin 1A receptors (5-HT1A) in the brain. This study was conducted to characterize the pharmacokinetics of [18F]mefway in rats and to establish the kinetic model for the binding of [18F]mefway to the 5-HT1A.

Methods [18F]Mefway was injected to the tail vein with or without pre-treatment of fluconazole i.v. infusion (60 mg/kg) and arterial blood samples were collected at several time points. Metabolite corrected plasma pharmacokinetic parameters were estimated by non-compartmental analysis. Dynamic PET scans were conducted over 120 min after intravenous injection of [18F]mefway with pre-treatment of fluconazole i.v. infusion. The binding potential values were estimated by the reference tissue models and the two tissue compartment model.

Results The parent fraction in rats was quickly decreased for 1hr after i.v. injection of [18F]mefway. After pre-treatment with fluconazole, the rate of decrease of the parent fraction was inhibited and the terminal half-life (t1/2) and the area under the time-concentration curve (AUC) were significantly increased from 0.80 ± 0.10 to 2.46 ± 0.20 hr and from 27.5 ± 6.5 to 78.9 ± 31.4 kBq.hr/mL, respectively. In addition, the systemic clearance (Cl) was significantly decreased from 2.12 ± 0.30 to 0.80 ± 0.21 L/hr. The non-displaceable binding potential (BPND) values of [18F]mefway to the 5-HT1A were estimated to 5.04 and 5.16 in the SRTM2 and MRTM2 model, respectively. In the two tissue compartment model analysis, K1, k2, k3, k4, and BP were estimated to 1.02 mL/cm3/min, 4.27 min-1, 0.855 min-1, 0.0783 min-1, and 15.5, respectively.

Conclusions The metabolic clearance of [18F]mefway was effectively decreased by pre-treatment with fluconazole in rats. The kinetic model for the binding of [18F]mefway to the 5-HT1A was established.

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Journal of Nuclear Medicine
Vol. 54, Issue supplement 2
May 2013
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Pharmacokinetics of [18F]mefway, a probe for brain serotonin 1A receptor imaging, in rats
Byoung Soo Kim, Jae Yong Choi, Eun Jung Kim, Dan Bee Choi, Chi Hoon Yi, Sang Jin Han, Young Hoon Ryu, Tae Hyun Choi
Journal of Nuclear Medicine May 2013, 54 (supplement 2) 1106;

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Pharmacokinetics of [18F]mefway, a probe for brain serotonin 1A receptor imaging, in rats
Byoung Soo Kim, Jae Yong Choi, Eun Jung Kim, Dan Bee Choi, Chi Hoon Yi, Sang Jin Han, Young Hoon Ryu, Tae Hyun Choi
Journal of Nuclear Medicine May 2013, 54 (supplement 2) 1106;
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