18F标记哒嗪酮类似物的制备及其在小鼠体内的生物分布

doi:10.7538/tws.2013.26.01.0023

同位素 ›› 2013, Vol. 26 ›› Issue (1): 23-28.DOI: 10.7538/tws.2013.26.01.0023

• 放射性药物和标记化合物 • 上一篇下一篇

¹⁸F标记哒嗪酮类似物的制备及其在小鼠体内的生物分布

彭程¹;牟甜甜^2,4;赵祚全²;马云川¹;张现忠^2,3

1.首都医科大学宣武医院 PET中心，北京100053；2.放射性药物教育部重点实验室，北京师范大学化学学院，北京100875；3. 分子影像暨转化医学研究中心，厦门大学公共卫生学院，厦门361005；4. 首都医科大学附属北京安贞医院核医学科，北京100029

出版日期:2013-02-20 发布日期:2013-03-18

Synthesis and Biodistribution of 2-tert-butyl-4-chloro-5-(2-[¹⁸F]fluroethoxy)-2H-pyridazin-3-one

PENG Cheng¹;MOU Tian-tian^2,4;ZHAO Zuo-quan²;MA Yun-chuan¹;ZHANG Xian-zhong^2,3

1. PET Center of Xuanwu Hospital, Capital University， Beijing 100053, China;2. Key Laboratory of Radiopharmaceuticals（Ministry of Education）, College of Chemistry, Beijing Normal University, Beijing 100875, China; 3. Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen 361005, China; 4. Department of Nuclear Medicine, Capital Medical University affiliated Beijing Anzhen Hospital, Beijing 100029， China

Online:2013-02-20 Published:2013-03-18

摘要/Abstract

摘要：

设计并合成了一种¹⁸F标记哒嗪酮类似物：2-特丁基-4-氯-5-(2氟[¹⁸F]乙氧基)-2H-3-哒嗪酮（¹⁸F-FP2），通过生物分布实验评价了其用于心肌灌注显像的可行性。¹⁸F-FP2的总制备时间为70～90 min，校正后的放化产率为53.0%±5.2%，放化纯度>98%；¹⁸F-FP2为脂溶性化合物，在水溶液中可稳定放置3 h以上。生物分布实验结果显示，¹⁸F-FP2在肝、肺中初期摄取高，注射后2 min分别为（14.53±2.36）%ID/g和（33.69±10.79）%ID/g，但清除很快，注射后15 min，其肝、肺的清除率已分别达57.7%和86.2%。¹⁸F-FP2的心肌摄取较低，最高摄取值为（4.09±0.53）%ID/g（注射后2 min）。这可能因标记侧链上未带苯环造成的，说明哒嗪酮侧链的芳环结构对心肌的摄取与滞留有较大影响。

关键词: ¹⁸F-FP2, 哒嗪酮, 心肌摄取, 生物分布

Abstract:

A fluorine-18 labeled pyridazinone derivative: 2-tert-butyl-4-chloro-5-(2-[¹⁸F]fluroethoxy)-2H-pyridazin-3-one (¹⁸F-FP2) was designed and prepared as a potential myocardial perfusion imaging agent. The total radiosynthesis time was 70-90 min, typical decay corrected radiochemical yield was 53.0%±5.2%, and the radiochemical purities were >98% after purification. It is a lipophilic compound, and stable in water for 3 h. The results of biodistribution studies in mice showed that ¹⁸F-FP2 had high liver and lung uptake at initial post injection time, the uptake was (14.53±2.36）%ID/g and (33.69±10.79）%ID/g at 2 min post injection, respectively. Radioactivity was washed out very fast from liver and lung, the rate of clearance was 57.7% and 86.2% at 15 min post-injection, respectively. However the heart uptake of ¹⁸F-FP2 was very low, the highest heart uptake was(4.09±0.53)%-ID/g at 2 min post injection. This may due to the removing of phenyl group in the labeling sidechain of pyridazinone, indicating that the aromatic ring has strong influence on the heart uptake and retention.

Key words: ¹⁸F-FP2, pyridazinone, heart uptake, biodistribution

彭程;牟甜甜;赵祚全;马云川;张现忠. ¹⁸F标记哒嗪酮类似物的制备及其在小鼠体内的生物分布[J]. 同位素, 2013, 26(1): 23-28.

PENG Cheng;MOU Tian-tian;ZHAO Zuo-quan;MA Yun-chuan;ZHANG Xian-zhong. Synthesis and Biodistribution of 2-tert-butyl-4-chloro-5-(2-[¹⁸F]fluroethoxy)-2H-pyridazin-3-one[J]. Journal of Isotopes, 2013, 26(1): 23-28.

参考文献

[1]Yu M, Guaraldi M, Kagan M, et al. Assessment of ¹⁸F-labeled mitochondrial complex I inhibitors as PET myocardial perfusion imaging agents in rats, rabbits, and primates [J]. European Journal of Nuclear Medicine and Molecular Imaging, 2009, 36: 63-72.

[2]Yalamanchili P, Wexler E, Hayes M, et al. Me-chanism of uptake and retention of F-18 BMS-747 158-02 in cardiomyocytes: a novel PET myocardial imaging agent [J]. Journal of Nuclear Cardiology, 2007, 14: 782-788.

[3]Huisman MC, Higuchi T, Reder S, et al. Initial Characterization of an ¹⁸F-Labeled Myocardial Perfusion Tracer [J]. Journal of Nuclear Medicine, 2008, 49: 630-636.

[4]Yu M, Guaraldi MT, Bozek J, et al. Effects of food intake and anesthetic on cardiac imaging and uptake of BMS747158-02 in comparison with FDG [J]. Journal of Nuclear Cardiology, 2009, 16: 763-768.

[5]Sherif HM, Saraste A, Weidl E, et al. Evaluation of a Novel ¹⁸F-Labeled Positron-Emission Tomography Perfusion Tracer for the Assessment of Myocardial Infarct Size in Rats / CLINICAL PERSPECTIVE [J]. Circulation: Cardiovascular Imaging, 2009, 2: 77-84.

[6]Yu M, Bozek J, Guaraldi M, et al. Cardiac imaging and safety evaluation of BMS747158, a novel PET myocardial perfusion imaging agent, in chronic myocardial compromised rabbits [J]. Journal of Nuclear Cardiology, 2010, 17: 631-636.

[7]Maddahi J, Czernin J, Lazewatsky J, et al. Phase I, First-in-Human Study of BMS747158, a Novel ¹⁸F-Labeled Tracer for Myocardial Perfusion PET: Dosimetry, Biodistribution, Safety, and Imaging Characteristics After a Single Injection at Rest [J]. Journal of Nuclear Medicine, 2011, 52: 1490-1498.

[8]Maddahi J, Bengel F, Huang SC, et al. Phase 1 rest-stress study of F-18 labeled BMS747158 myocardial perfusion PET tracer: Human safety, dosimetry, biodistribution, and myocardial imaging characteristics [J]. Journal of Nuclear Medicine, 2009, 50: 184-184.

[9]Sherif HM, Nekolla SG, Saraste A, et al. Simplified Quantification of Myocardial Flow Reserve with flurpiridaz F 18: Validation with Microspheres in a Pig Model [J]. Journal of Nuclear Medicine, 2011, 52: 617-624.

[10]Mou T, Zhao Z, Fang W, et al. Synthesis and Preliminary Evaluation of ¹⁸F-labeled Pyridaben Analogues for Myocardial Perfusion Imaging with Positron Emission Tomography [J]. Journal of Nuclear Medicine, 2012, 53: 472-479.

[11]Purohit A, Radeke H, Azure M, et al. Synthesis and Biological Evaluation of Pyridazinone Analogues as Potential Cardiac Positron Emission Tomography Tracers [J]. Journal of Medicinal Chemistry, 2008, 51: 2954-2970.

[12]Mou T, Zhao Z, Yang W, et al. Radiosynthesis and biodistribution of [¹⁸F]FPTP2 as potential myocardial perfusion imaging agent [J]. Journal of Labelled Compounds and Radiopharmaceuticals, 2011, 54: S446.

[13]Mou T, Jing H, Yang W, et al. Preparation and biodistribution of [¹⁸F]FP2OP as myocardial perfusion imaging agent for positron emission tomography [J]. Bioorganic & Medicinal Chemistry, 2010, 18: 1312-1320.

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¹⁸F标记哒嗪酮类似物的制备及其在小鼠体内的生物分布

Synthesis and Biodistribution of 2-tert-butyl-4-chloro-5-(2-[¹⁸F]fluroethoxy)-2H-pyridazin-3-one

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