氟[18F]脱氧葡糖注射液中三甲基硅醇杂质的毒性研究

doi:10.19803/j.1672-8629.20240571

摘要/Abstract

摘要： 目的以斑马鱼胚胎及幼鱼为实验对象,研究氟[¹⁸F]脱氧葡糖注射液（FDG）中工艺引入杂质三甲基硅醇对斑马鱼胚胎及幼鱼的影响,以评估其毒性。方法采用体视光学显微镜观察给予三甲基硅醇后斑马鱼胚胎及幼鱼的发育情况,包括致畸和致死检测;应用斑马鱼行为轨迹跟踪系统评价三甲基硅醇对斑马鱼幼鱼自主行为的影响。结果三甲基硅醇可剂量依赖性地降低斑马鱼胚胎及幼鱼的存活率,增加畸形率;不仅可显著抑制胚胎卵黄囊吸收和幼鱼浮漂生长,还能引发胚胎和幼鱼围心囊水肿,此外还可显著导致幼鱼行为活跃。结论三甲基硅醇对斑马鱼胚胎及幼鱼表现出显著的发育毒性和心脏毒性,还对幼鱼表现出一定程度的神经毒性,应在FDG产品中对其进行严格控制。

关键词: 氟[¹⁸F]脱氧葡糖, 注射液, 三甲基硅醇, 斑马鱼, 发育, 心脏, 神经, 毒性

Abstract: Objective To explore the toxicity of trimethylsilanol, which is an impurity introduced into fludeoxyglucose [¹⁸F] injection, on zebrafish embryos and larvae. Methods The development of zebrafish embryos and larvae exposed to different concentrations of trimethylsilanol was observed by stereomicroscopy, involving teratogenic and lethal detection. The trajectory tracking system for zebrafish behavior was used to analyze the influence of trimethylsilanol on autonomous behavior of larvae. Results Trimethylsilanol led to a dose-dependent decrease of survival of zebrafish embryos and larvae, induced an increase in deformity and edema of pericardial sac in both embryos and larvae, inhibited embryo yolk sac absorption and larvae floating growth, and activated the behavior of larvae. Conclusion Trimethylsaline has not only significant developmental and cardiac toxicity on the embryos and larvae of zebrafish, but also some neural toxicity on the larvae.

Key words: Fludeoxyglucose[¹⁸F], Injection, Trimethylsilanol, Zebrafish, Development, Cardiac System, Neural System, Toxicity

中图分类号:

R915
R994

孟祥慧, 孙葭北, 李文龙, 贾娟娟, 程茗, 黄海伟, 施亚琴. 氟[¹⁸F]脱氧葡糖注射液中三甲基硅醇杂质的毒性研究[J]. 中国药物警戒, 2025, 22(4): 397-402.

MENG Xianghui, SUN Jiabei, Li Wenlong, JIA Juanjuan, CHENG Ming, HUANG Haiwei, SHI Yaqin. Zebrafish Toxicity of Trimethylsilanol: an Introduced Impurity in Fludeoxyglucose [¹⁸F] Injection[J]. Chinese Journal of Pharmacovigilance, 2025, 22(4): 397-402.

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https://zgywjj.magtechjournal.com/CN/Y2025/V22/I4/397

参考文献

[1] Chinese Pharmacopoeia Commission.Pharmacopoeia of the People’s Republic of China, Volume II(中华人民共和国药典二部)[M]. Beijing: China Medical Science Press, 2020.
[2] JIA JJ, SUN DY, CHENG M, et al.Unknown Impurities Trimethylsilanol in Fludeoxyglucose [¹⁸F] Injection[J]. Journal of Isotopes(同位素), 2023, 36(2): 198-202.
[3] RAICH MJ, RIBAS FC, DE AN, et al.Analytical Methodology for Sampling and Analyzing Eight Siloxanes and Trimethylsilanol in Biogas from Different Wastewater Treatment Plants in Europe[J]. Analytica Chimica Acta, 2014, 17(812): 83-91.
[4] SIGMA-ALDRICH.Trimethylsilanol-SAFETY DATA SHEET 2024[EB/OL]. (2017-05-26)[2024-07-30]. https://www.sigmaaldrich.cn/CN/zh/sds/aldrich/725986?userType=anonymous.
[5] ISQUITH A, SLESINSKI R, MATHESON D.Genotoxicity Studies on Selected Organosilicon Compounds: in vivo Assays[J]. Food and Chemical Toxicology, 1988, 26(3):263-266.
[6] ECHA. Hexamethyldisiloxane, 2017[EB/OL]. (2017-06-20)[2024-07-30]. https://echa.europa.eu/de/registration-dossier/-/registered-dossier/15156.
[7] WEN ZC, ZHANG KJ, XU JC, et al.Novel Animal and Non-Animal Cardiac Safety Evaluation Models[J]. Chinese Journal of New Drugs and Clinical Remedies(中国新药与临床杂志), 2024, 43(5): 333-338.
[8] LI W, LI XB, DONG YQ, et al.Cardiovascular Activity of Five Glycyrrhizic Acid Drugs Based on Zebrafish Model[J]. Drug Evaluation Research, 2024, 47(9): 1995-2005.
[9] LU YQ, SHANG XM, WANG J, et al.Current Progress of Zebrafish Model in Autism Spectrum Disorder[J]. Biotechnology(生物技术), 2024, 34(1): 126-133.
[10] SURESH KV, ADITYA N, ADRIJIA S, et al.Zebrafish (Danio rerio) as an Ecotoxicological Model for Nanomaterial Induced Toxicity Profiling[J]. Precision Nanomedicine, 2021, 4(1): 750-782.
[11] ZHANG Q, SHEN Y, ZHAO X, et al.Genotoxicity of Lansoprazole’s Related Impurities[J]. Chinese Pharmaceutical Journal(中国药学杂志), 2023, 58(23): 2165-2171.
[12] ZENG B, ZHANG CY, CHEN K.Application and Research Progress of Model Biological Zebrafish in Drug Toxicity Evaluation[J]. Natural Product Research and Development(天然产物研究与开发), 2020, 32: 1794-1801.
[13] LI HY, XIE Q, WANG C, et al.Research Progress on Application and Mechanism of Zebrafish in Drug Toxicology Assessment[J]. Chinese Traditional and Herbal Drugs(中草药), 2021, 52(1): 278-287.
[14] ZHANG MQ, ZHANG JP, HU CQ.Comparative Analysis of Gastrointestinal Toxicity Induced by Cefazolin and Its Impurities in Zebrafish[J]. Chinese Journal of Antibiotics(中国抗生素杂志), 2024, 49(3): 317-324.
[15] ZHANG R, MA YY, HAN Y, et al.Toxicity of Ceftriaxone and Its Impurities to the Liver of Zebrafish[J]. Carcinogenesis, Teratogenesis & Mutagenesis(癌变·畸变·突变), 2024, 36(1): 35-47.
[16] WANG BJ, FU LB, YE XN, et al.Cardiac and Neural Toxicity and Mechanisms of Fentanyl in Zebrafish Larve[J]. Chinese Journal of Pharmacology and Toxicology(中国药理学与毒理学杂志), 2023, 37(10): 767-773.
[17] CASSAR S, ADATTO I, FREEMAN J L, et al.Use of Zebrafish in Drug Discovery Toxicology[J]. Chemical Research in Toxicology, 2020, 33(1): 95-118.
[18] WANG J, LIU L, XU YJ, et al.Application of Zebrafish by High-Throughput Methods in Toxicity Assessment of Chemicals[J]. Environmental Chemistry(环境化学), 2024, 43(1): 47-59.
[19] FDA. Guide for the Care and Use of Laboratory Animals[EB/OL].(2024-06-01)[2024-07-30]. https://olaw.nih.gov/sites/default/files/Guide-for-the-Care-and-Use-of-Laboratory-Animals.pdf.
[20] HE JH, GAO JM, HUANG CJ, et al.Zebrafish Models for Assessing Developmental and Reproductive Toxicity[J]. Neurotoxicology and Teratology, 2014, 42: 35-42.
[21] WU ZJ, CHEN SY, ZHENG L.Sulforaphane Attenuates Ethanol-Induced Teratogenesis and Dysangiogenesis in Zebrafish Embryos[J]. International Journal of Molecular Sciences, 2024, 25: 11529.
[22] MANIKANDAN P, SARMAH S, MARRS JA.Ethanol Effects on Early Developmental Stages Studied Using the Zebrafish[J]. Biomedicines, 2022, 10, 2555.
[23] COLLIER AD, ABDULAI AR, LEIBOWITZ SF.Utility of the Zebrafish for Studying Neuronal and Behavioral Disturbances Induced by Embryonic Exposure to Alcohol, Nicotine and Cannabis[J]. Cells, 2023, 12, 2505.
[24] CARLY L, CLAYMAN, VICTORIA PC.Neurochemical and Behav-ioral Consequences of Ethanol and/or Caffeine Exposure: Effects in Zebrafish and Rodents[J]. Current Neuropharmacology, 2022, 20, 560-578.
[25] QI Y, XU H, LI XY, et al.Silica Nanoparticles Induce Cardiac Injury and Dysfunction via ROS/Ca²+/Ca MKII Signaling[J]. Science of the Total Environment, 2022, 10, 1205.
[26] LIU P, WANG S, CHANG ZM, et al. Combined Toxicity of Silica Nanoparticles and Cadmium Chloride on the Cardiovascular System of Zebrafish (Danio Rerio) Larve[J]. Comparative Biochemistry and Physiology, 2021, Part C 239: 108895.
[27] LI X, DANG J, LI Y, et al.Developmental Neurotoxicity Fingerprint of Silica Nanoparticles at Environmentally Relevant Level on Larval Zebrafish Using a Neurobehavioral-Phenomics-Based Biological Warning Method[J]. Science of Total Environment, 2021, 752, 141878.
[28] WEI JL, LIU JH, LIANG S, et al.Low-Dose Exposure of Silica Nanoparticles Induces Neurotoxicity via Neuroactive Ligand-Receptor Interaction Signaling Pathway in Zebrafish Embryos[J]. International Journal of Nanomedicine, 2020, 15: 4407-4415.
[29] VRANIC S, SHIMADA Y, ICHIHARA S, et al.Toxicological Evaluation of SiO₂ Nanoparticles by Zebrafish Embryo Toxicity Test[J]. International Journal of Molecular Sciences, 2019, 20(4): 882.
[30] FAIN JH, GAD S.Silicones[J]. Encyclopedia of Toxicology, 2014, 4: 270-272.

氟[¹⁸F]脱氧葡糖注射液中三甲基硅醇杂质的毒性研究

Zebrafish Toxicity of Trimethylsilanol: an Introduced Impurity in Fludeoxyglucose [¹⁸F] Injection

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