Lee, Hak Jeong
(Department of Nuclear Medicine, Seoul National University College of Medicine and Institute of Radiation Medicine, Medical Research Center)
,
Jeong, Jae Min
(Department of Nuclear Medicine, Seoul National University College of Medicine and Institute of Radiation Medicine, Medical Research Center)
,
Lee, Sang-Yoon
(Neuroscience Research Institute, Gachon University)
,
Ido, Tatsuo
(Neuroscience Research Institute, Gachon University)
Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tertrahydro-N-methyl-1-naphthalenamine (sertraline) hydrochloride from among selective serotonin reuptake inhibitors (SSRIs) is a treatment of major depression. For the differential diagnosis by metabolizing serotonin in a patient with neurological disorder...
Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tertrahydro-N-methyl-1-naphthalenamine (sertraline) hydrochloride from among selective serotonin reuptake inhibitors (SSRIs) is a treatment of major depression. For the differential diagnosis by metabolizing serotonin in a patient with neurological disorders, the radiolabeled $^{11}C$-sertraline was developed for non-invasive positron emission tomography in living brain and use the evaluation of new drug for SSRIs. We release the results of a fast and easy radiolabeling method applied a one-step loop method with $[^{11}C]CH_3OTf$ for routine clinical applications of $^{11}C$-sertraline. 1 mg of a precursor for $^{11}C$-sertraline in 0.1 mL DMF and $5{\mu}L$ of 1N NaOH, were injected into the loop of semi-prep high-performance liquid chromatography (HPLC). $[^{11}C]CH_3OTf$ was passed through the loop at room temperature (RT). The $^{11}C$-sertraline was separated by the semi-preparative HPLC. $^{11}C$-sertraline was eluted at 28.0 min was collected and evaluated by analytical HPLC and mass spectrometer. The total radiolabeling efficiency of $^{11}C$-sertraline was $30.7{\pm}8.7%$. The specific activity was $64.8{\pm}51.4GBq/{\mu}mol$. The radiochemical and chemical purities were higher than 99%. The mass spectrum of the product showed m/z peaks at 307.1 (M+1), indicating the mass of sertraline. By the one-step loop method with $[^{11}C]CH_3OTf$, $^{11}C$-sertraline could be quickly and easily prepared for clinical application.
Cis-(1S,4S)-4-(3,4-dichlorophenyl)-1,2,3,4-tertrahydro-N-methyl-1-naphthalenamine (sertraline) hydrochloride from among selective serotonin reuptake inhibitors (SSRIs) is a treatment of major depression. For the differential diagnosis by metabolizing serotonin in a patient with neurological disorders, the radiolabeled $^{11}C$-sertraline was developed for non-invasive positron emission tomography in living brain and use the evaluation of new drug for SSRIs. We release the results of a fast and easy radiolabeling method applied a one-step loop method with $[^{11}C]CH_3OTf$ for routine clinical applications of $^{11}C$-sertraline. 1 mg of a precursor for $^{11}C$-sertraline in 0.1 mL DMF and $5{\mu}L$ of 1N NaOH, were injected into the loop of semi-prep high-performance liquid chromatography (HPLC). $[^{11}C]CH_3OTf$ was passed through the loop at room temperature (RT). The $^{11}C$-sertraline was separated by the semi-preparative HPLC. $^{11}C$-sertraline was eluted at 28.0 min was collected and evaluated by analytical HPLC and mass spectrometer. The total radiolabeling efficiency of $^{11}C$-sertraline was $30.7{\pm}8.7%$. The specific activity was $64.8{\pm}51.4GBq/{\mu}mol$. The radiochemical and chemical purities were higher than 99%. The mass spectrum of the product showed m/z peaks at 307.1 (M+1), indicating the mass of sertraline. By the one-step loop method with $[^{11}C]CH_3OTf$, $^{11}C$-sertraline could be quickly and easily prepared for clinical application.
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제안 방법
The collected 11C-sertraline was analyzed by analytical HPLC (Column: Waters XBridgeTM RP-18, 4.6 X 100 mm, 3.5 μm; Waters, Milford, Ma, U.S.A.; Eluent: 35% MeCN in D.W.(Both contained 0.05% TFA) ; flow rate: 1 mL/min; UV: 215 nm).
The precursor of 11C-sertraline was prepared with synthesizing the cis form of norsertraline. This study could improve the performance by applying the radiolabeling method of 11C-sertraline with [11C]CH3OTf by the fast and easy loop method compared with the conventional method using [11C]CH3I. The previous radiolabeling reaction by the method with [11C]CH3I was heated to 120 °C for 8 min.
대상 데이터
Captured [11C]CH3I in a reaction vial heated for evaporation at 120ºC. The [11C]CH3I gas was blown by N2 gas (99.999%) and passed through each cartridges filled with Mg(ClO4)2 and Na2HPO4. for drying moisture.
이론/모형
The automatic 11C-methylation module, reported in the previous paper (18), was used for the radiosynthesis of 11C-sertraline applied with the loop method (12). 1 mg of norsertraline separated in 4 mL vial was dissolved in DMF 0.
참고문헌 (18)
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Iwata R, Pascali C, Yuasa M, Yanai K, Takahashi T, Ido T. On-line [ $^{11}C$ ]methylation using [ $^{11}C$ ]methyl iodide for the automated preparation of $^{11}C$ -radiopharmaceuticals. Applied Radiation and Isotopes 1992;43:1083-8.
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Iwata R, Pascali C, Bogni A, Miyake Y, Yanai K, Ido T. A simple loop method for the automated preparation of [ $^{11}C$ ] raclopride from [ $^{11}C$ ]methyl triflate. Applied Radiation and Isotopes 2001;55:17-22.
Han Z, Koenig SG, Zhao H, Su X, Singh SP, Bakale RP. Development of a Large-Scale Stereoselective Process for (1R,4S)-4-(3,4-Dichlorophenyl)-1,2,3,4-tetrahydronaphthalen- 1-amine Hydrochloride. Organic Process Research & Development 2007;11:726-30.
Pavese N, Gerhard A, Tai YF, Ho AK, Turkheimer F, Barker RA, Brooks DJ, Piccini P. Microglial activation correlates with severity in Huntington disease: a clinical and PET study. Neurology 2006;66:1638-43.
Lee HJ, Jeong JM, Lee Y, Kim HW, Lee E, Lee DS, Chung J, Lee MC. Radiosynthesis of [ $^{11}C$ ]6-OH-BTA-1 in Different Media and Confirmation of Reaction Byproducts. Nucl Med Mol Imaging 2007;41:241-6.
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