Optimization of the Radiosynthesis of the Dopamine Transporter Imaging Agent of 11C-β-CFT

doi:10.7538/tws.2018.31.05.

Abstract

Abstract:

The optimization for high synthesis yield was designed with ¹¹C-Triflate-CH₃I as methylation agent for dopamine transporter imaging agent of ¹¹C-β-CFT. The influence factors of the synthesis process were discussed, and the optimum synthetic conditions were established. In the paper, the study showed that the amount of precursor, the irradiation time, eluated condition, the reaction solvent etc could effect the synthetic efficiency. ¹¹C-β-CFT was automatic synthesized on PET-CM-3H-IT-Ⅰ with the optimum process conditions as the irradiation time 10-24 minutes, 0.5-1.0 g/L of precursor in 0.2 mL acetone: acetonitrile(1∶1, V∶V) and room temperature. We obtained a radiochemical yield of (76.93±6.49)% (n=76, ¹¹C-Triflate-CH₃ EOB). The radiochemical purity of final products were over 97%. The specific activities of final products were over （56.26±1.55） TBq/g. It took 16 minutes from ¹¹C-CO₂ to ¹¹C-β-CFT and the radio activity of ¹¹C-β-CFT were (8.07±1.94) GBq (n=76). By optimization of the technological conditions, the target product was suitable for clinical, the synthetic process was reliable and full automated, the product yield was improved and the residual problem of Sep-Pak C18 was resloved.

Key words: ¹¹C-β-CFT, full automated synthesis, PET/CT, quality control

摘要：

本文以¹¹C-Triflate-CH₃为甲基化试剂合成多巴胺转运蛋白显像剂¹¹C-β-CFT，探讨¹¹C-β-CFT合成效率的影响因素，优化合成条件，提高其合成效率。使用国产合成模块PET-CM-3H-IT-Ⅰ全自动化合成¹¹C-β-CFT，通过研究合成过程中反应溶剂、轰靶时间、前体量及淋洗终产品条件等影响因素，得到优化后¹¹C-β-CFT的生产条件：轰靶时长10～24 min,前体浓度为0.5～1.0 g/L，以0.2 mL体积比V（丙酮）∶V（乙腈）=1∶1为溶剂，反应条件为室温。从传输¹¹C-CO₂到终产品的总合成时间为16 min，产量为（8.07±1.94） GBq(n=76)；此条件下¹¹C-β-CFT的合成效率为(76.93±6.49)%(n=76,¹¹C-Triflate-CH₃校正效率)，产品的放化纯度大于97%，比活度(56.26±1.55) TBq/g。优化后的生产条件可以提高¹¹C-β-CFT合成效率，解决了Sep-Pak C18柱残留产品过多的问题，可实现稳定、全自动化合成¹¹C-β-CFT且保证产品满足临床需求。

关键词: ¹¹C-β-CFT, 全自动化合成, PET/CT, 质量控制

LI Haifeng;XU Rengen;LI Yungang;CHEN Zhijun;ZHANG Xiaojun;ZHANG Jinming. Optimization of the Radiosynthesis of the Dopamine Transporter Imaging Agent of ¹¹C-β-CFT[J]. Journal of Isotopes, 2018, 31(5): 304-309.

李海峰;徐仁根;李云钢;陈志军;张晓军;张锦明. 探讨多巴胺转运蛋白显像剂¹¹C-β-CFT合成效率的影响因素[J]. 同位素, 2018, 31(5): 304-309.

References

［1］Yagi S, Yoshikawa E, Futatsubashi M, et al. Progression from unilateral to bilateral parkinsonism in early Parkinson disease: implication of mesocortical dopamine dysfunction by PET［J］. J Nucl Med, 2010, 51(8): 1250-1257.
［2］Kono S, Shirakawa K, Ouchi Y, et al. Dopaminergic neuronal dysfunction associated with parkinsonism in both a Gaucher disease patient and a carrier［J］. J Neurol Sci, 2007, 252(2): 181-184.
［3］Park E, Hwang Y M, Lee C N, et al. Differential diagnosis of patients with inconclusive Parkinsonian features using ［¹⁸F］FP-CIT PET/CT［J］. Nucl Med Mol Imaging, 2014, 48(2): 106-113.
［4］Fukae J, Fukaya C, Oshima H, et al. Successful treatment with bilateral deep brain stimulation of the subthalamic nucleus for benign tremulous parkinsonism［J］. Rinsho Shinkeigaku, 2014, 54(6): 511-414.
［5］Konishi T, Kono S, Fujimoto M, et al. Benign hereditary chorea: dopaminergic brain imaging in patients with a novel intronic NKX2.1 gene mutation［J］. J Neurol, 2013, 260(1): 207-213.
［6］Rinne J O, Laihinen A, Nagren K, et al. PET examination of the monoamine transporter with ［¹¹C］beta-CIT and ［¹¹C］beta-CFT in early Parkinson's disease［J］. Synapse, 1995, 21(2): 97-103.
［7］Ouchi Y, Kanno T, Okada H, et al. Presynaptic and postsynaptic dopaminergic binding densities in the nigrostriatal and mesocortical systems in early Parkinson's disease: a double-tracer positron emission tomography study［J］. Ann Neurol,1999, 46(5): 723-731.
［8］Yoder K K, Hutchins G D, Mock B H, et al. Dopamine transporter binding in rat striatum: a comparison of ［O-methyl-¹¹C］beta-CFT and ［N-methyl-¹¹C］beta-CFT［J］. Nucl Med Biol, 2009, 36(1): 11-16.
［9］Kawamura K, Oda K, Ishiwata K. Age-related changes of the ［¹¹C］CFT binding to the striatal dopamine transporters in the Fischer 344 rats: a PET-study［J］. Ann Nucl Med, 2003,17(3): 249-253.
［10］Liu L, Zhang W, Gong X, et al. Relation between microPET imaging and rotational behavior in a parkinsonian rat model induced by medial forebrain bundle axotomy［J］. Behav Brain Res, 2014, 265: 148-154.
［11］Saiki H, Hayashi T, Takahashi R, et al. Objective and quantitative evaluation of motor function in a monkey model of Parkinson's disease［J］. J Neurosci Methods, 2010,190(2): 198-204.
［12］Zhang Y F, Wang X Y, Cao L, et al. Effects of hypoxic-ischemic brain injury on striatal dopamine transporter in newborn piglets: evaluation of ¹¹C-CFT PET/CT for DAT quantification［J］. Nucl Med Biol, 2011, 38(8): 1205-1212.
［13］Ishibashi K, Oda K, Ishiwata K, et al. Comparison of dopamine transporter decline in a patient with Parkinson's disease and normal aging effect［J］. J Neurol Sci, 2014, 339(1-2): 207-209.
［14］文富华，邓怀福，王红亮，等. 多巴胺转动蛋白显像剂¹¹C-β-CFT的全自动化合成［J］. 同位素，2014，24(4):193-197.Wen Fuhua, Deng Huaifu, Wang Hongliang, et al. Full automated synthesis of ¹¹C-β-CFT as a dopamine transporter imaging agent［J］. Journal of Isotopes, 2014, 24(4):193-197（in Chinese）.
［15］张锦明，田嘉禾，郭喆,等. 在线自动化制备多巴胺转运蛋白显像剂¹¹C-β-CFT［J］. 中华核医学杂志,2005,25(3):142-145.Zhang Jinming, Tian Jiahe, Guo zhe, et al. Automated on-line preparation of ¹¹C-β-CFT, a dopamine transporter imaging agent［J］. Chin J Nucl Med, 2005, 25(3): 142-145（in Chinese）.
［16］李海峰，陈志军，张晓军，等. ¹¹C-标记雷氯必利合成效率的影响因素［J］. 同位素，2016,29(1):12-18.Li Haifeng, Chen Zhijun, Zhang xiaojun, et al. Optimization of the synthetic efficiency of the ¹¹C-Raclopride［J］. Journal of Isotopes, 2016, 29(1): 12-18（in Chinese）.

[1]	ZHOU Ming;LI Yulai;YANG Neng’an;LI Jian;CHEN Xiaojuan;HU Shuo. Modified Synthesis and Clinical Trial of ［¹⁸F］-Phe-BF₃ [J]. Journal of Isotopes, 2020, 33(3): 167-172.
[2]	WEN Fuhua;ZHANG Zhanwen;Ma Hui;ZHANG Dake;TANG Ganghua. Full Automated Synthesis of ¹⁸F-FDOPA and Preliminary PET/CT Imaging [J]. Journal of Isotopes, 2018, 31(5): 269-275.
[3]	ZHANG Xiaojun;FU Huaping;LI Yungang;LIU Jian;HE Yulin;LIU Yachao;XU Baixuan;ZHU Hong;WU Jiang;CUI Mengchao;ZHANG Jinming. Preparation and Clinical Application of ¹⁸F-DCFPyL [J]. Journal of Isotopes, 2018, 31(5): 291-297.
[4]	LI Qi-ming;JIN Rong-bing;WANG Fang-yang;TANG Yi;YAO Zhi-peng. Synthesis and Quality Control of the PET Radiotracer ¹¹C-Flumazenil [J]. Journal of Isotopes, 2017, 30(1): 16-22.
[5]	LI Hai-feng;CHEN Zhi-jun;ZHANG Xiao-jun;LI Yun-gang;ZHANG Jin-ming. Optimization for the Synthesis Efficiency of the ¹¹C-Raclopride [J]. Journal of Isotopes, 2016, 29(1): 12-18.
[6]	FU Bo;WANG Xiao-jing;YE Zhao-yun;ZHANG Yun;ZHANG Wen-zai. Quality Control Standard of Samarium Sm-153 Lexidronam Injection [J]. Journal of Isotopes, 2015, 28(3): 140-147.
[7]	ZHANG Xiao-jun;LIU Jian;LI Yun-gang;TIAN Jia-he;ZHANG Jin-ming. Automatic Synthesis and Micro PET/CT Imaging Study of ¹¹C-DASB as a Serotonin Imaging Agent [J]. Journal of Isotopes, 2015, 28(1): 1-6.
[8]	ZHANG Jin-ming;ZHANG Xiao-jun;LI Yun-gang;LIU Jian;XU Bai-xuan;WANG Rui-min;TIAN Jia-he. Automatic Synthesis and Quality Control of ¹¹C-Raclopride for Clinical Use [J]. Journal of Isotopes, 2014, 27(4): 230-235.
[9]	ZHANG Xiao-jun;XIANG Xiao-hui;ZHANG Jin-ming;TIAN Jia-he. Quality Control of ¹¹C-Carfentanil [J]. Journal of Isotopes, 2013, 26(1): 29-32.
[10]	LU Guo-xiu;ZHANG Cai-xia;XU Wei-na;YU Shu-peng;XIN Jun. ¹⁸F-FDG PET/CT Imaging in Diagnosing and Prognosticating Malignant Pleutal Mesothelioma [J]. Journal of Isotopes, 2012, 25(1): 58-63.
[11]	XIE Bo-qia;YANG Min-fu;YE Jue;YANG Zi-he;DOU Ke-fei;HAN Chun-lei;TIAN Yi. Experimental Study of the Molecular Mechnisms of Myocardial Ischemic Memory With ¹⁸F-FDG PET/CT Imaging [J]. Journal of Isotopes, 2012, 25(1): 47-52.
[12]	. Direct measurement of Kryptofix 2.2.2 in 18F-FDG by Gas Chromatography [J]. Journal of Isotopes, 2007, 20(2): 105-108.
[13]	. Radiation Protection and Quality Control in the Reconstructing Progress on Radiation Work Site [J]. Journal of Isotopes, 2005, 18(3 ): 189-189 .
[14]	. Preparation and Quality Control of ~(188)W-~(188)Re Generator [J]. Journal of Isotopes, 2004, 17 (4 ): 210-210 .
[15]	. Application of Single Background Quality Control Chart in Montioring the Long-term Stability of RIA Counter [J]. Journal of Isotopes, 2004, 17 (2 ): 122-122 .

Optimization of the Radiosynthesis of the Dopamine Transporter Imaging Agent of ¹¹C-β-CFT

探讨多巴胺转运蛋白显像剂¹¹C-β-CFT合成效率的影响因素

PDF

Knowledge

Abstract

Cite this article

share this article

References

Related Articles 15

Recommended Articles

Metrics