诊断用碘[~(131)I]苄胍中试生产工艺研究
|
摘要
目的探索最佳的诊断用碘[~(131)I]苄胍注射液中试生产工艺参数。方法采用Cu SO4催化法进行碘苄胍的~(131)I标记,纸色层法测定标记物的标记率,评价标记物的体外稳定性。结果优选的碘[~(131)I]苄胍的中试生产工艺参数为:抗坏血酸95~100mg、Cu SO4·5H2O 6~8mg、碘苄胍40~50mg、Na~(131)I溶液55.5~74GBq;反应液经0.3mol/L H2SO4溶液调节p H至1~3后于110~120℃下反应35min。碘[~(131)I]苄胍标记率和收率分别95%~99%、70%~75%。稳定性结果显示,标记物在干冰保存条件下的体外稳定性较好,放置15d后放射化学纯度降低不超过1%。结论以上结果提示,碘[~(131)I]苄胍中试生产工艺参数可控,重现性较好,为规模化碘[~(131)I]苄胍生产提供了数据支持。
Objective To study the optimal parameters for ~(131)I-MIBG pilot production. Methods MIBG was labeled with~(131)I catalyzed by CuSO4. The labeling yield,determined by paper chromatography,was used to evaluate in vitro stability of the labels. Results The preferred ~(131)I-MIBG pilot production process parameters were as follows; 95-100 mg ascorbic acid,6-8 mg CuSO4·5 H2 O,40-50 mg MIBG and 55. 5-74 GBq Na~(131)I solution; The reaction liquid was adjusted to pH 1-3 by 0. 3 mol/L of H2 SO4 solution and then reacted at110-120℃ for 35 minutes. The labeling yield and the yield rate were 95%-99% and 70%-75%,respectively. The results of the stability tests demonstrated that in vitro stability of the labels stored in the dry ice was well accepted and the radiochemical purity was decreased by less than 1% after conserving for 15 days. Conclusion Our results indicated that the ~(131)I-MIBG pilot production process was well controlled with a good reproducibility,which provided data support for large-scale of ~(131)I-MIBG production.
Objective To study the optimal parameters for ~(131)I-MIBG pilot production. Methods MIBG was labeled with~(131)I catalyzed by CuSO4. The labeling yield,determined by paper chromatography,was used to evaluate in vitro stability of the labels. Results The preferred ~(131)I-MIBG pilot production process parameters were as follows; 95-100 mg ascorbic acid,6-8 mg CuSO4·5 H2 O,40-50 mg MIBG and 55. 5-74 GBq Na~(131)I solution; The reaction liquid was adjusted to pH 1-3 by 0. 3 mol/L of H2 SO4 solution and then reacted at110-120℃ for 35 minutes. The labeling yield and the yield rate were 95%-99% and 70%-75%,respectively. The results of the stability tests demonstrated that in vitro stability of the labels stored in the dry ice was well accepted and the radiochemical purity was decreased by less than 1% after conserving for 15 days. Conclusion Our results indicated that the ~(131)I-MIBG pilot production process was well controlled with a good reproducibility,which provided data support for large-scale of ~(131)I-MIBG production.
引文
[1]CARRASQUILLO JA,PANDIT-TASKAR N,CHEN C C,et al.I-131 metaiodobenzylguanidine therapy ofpheochromocytoma and paraganglioma[J].Semin Nucl Med,2016,46(3):203-214.
[2]PFLUGER T,PICCARDO A.Neuroblastoma;MIBG imaging and new tracers[J].Semin Nucl Med,2017,47(2):143-157.
[3]高云朝.嗜铬细胞瘤诊断进展[J].标记免疫分析与临床,2007,14(4):256-258.
[4]陈阳,黄东生,郑宇,等.131I标记间碘苄胍治疗神经母细胞瘤的疗效和安全性评价[J].中国小儿血液与肿瘤,2010,15:262-264.
[5]唐锁勤.高危神经母细胞的治疗[J].中国当代儿科杂志,2014,16(2):103-107.
[6]KIERNAN C M,SOLRZANO C C.Pheochromocytoma and paraganglioma;diagnosis,genetics,and treatment[J].Surg Oncol Clin N Am,2016,25(1):119-138.
[7]霍艳雷,王丹阳,王辉,等.放射性碘标记MIBG在儿童神经母细胞瘤诊治中的应用[J].中华核医学与分子影像杂志,2017,37(3):173-176.
[8]金从军,邵玉军,曾正陪,等.131I-间位碘代苄胍治疗恶性嗜铬细胞瘤/副神经节瘤的临床疗效分析[J].中华泌尿外科杂志,2015,36(1):24-28.
[9]张锦明,陈白薇,田嘉禾.β受体显像剂—碘(131)标记间碘苄胍标记方法的研究[J].军事进修学院学报,1994,15(2):124-126.
[10]Prabhakar G,Mehra K S,Ramamoorthy N,et al.Evaluation of radioiodination of meta-iodobenzylguanidine(MIBG)catalyzed by in situ generated Cu(I)and directly added Cu(II)[J].Appl Radiat Isot,1999,50(6):1011-1014.
[11]陈宝军,陈大明,杨红伟,等.123I-MIBG的制备及动物实验研究[J].原子能科学技术,2010,44(11):1299-1302.
[12]张锦明,田嘉禾,金小海,等.131I-间碘苄胍稳定性的研究[J].同位素,1996,9(4):219-222.
[2]PFLUGER T,PICCARDO A.Neuroblastoma;MIBG imaging and new tracers[J].Semin Nucl Med,2017,47(2):143-157.
[3]高云朝.嗜铬细胞瘤诊断进展[J].标记免疫分析与临床,2007,14(4):256-258.
[4]陈阳,黄东生,郑宇,等.131I标记间碘苄胍治疗神经母细胞瘤的疗效和安全性评价[J].中国小儿血液与肿瘤,2010,15:262-264.
[5]唐锁勤.高危神经母细胞的治疗[J].中国当代儿科杂志,2014,16(2):103-107.
[6]KIERNAN C M,SOLRZANO C C.Pheochromocytoma and paraganglioma;diagnosis,genetics,and treatment[J].Surg Oncol Clin N Am,2016,25(1):119-138.
[7]霍艳雷,王丹阳,王辉,等.放射性碘标记MIBG在儿童神经母细胞瘤诊治中的应用[J].中华核医学与分子影像杂志,2017,37(3):173-176.
[8]金从军,邵玉军,曾正陪,等.131I-间位碘代苄胍治疗恶性嗜铬细胞瘤/副神经节瘤的临床疗效分析[J].中华泌尿外科杂志,2015,36(1):24-28.
[9]张锦明,陈白薇,田嘉禾.β受体显像剂—碘(131)标记间碘苄胍标记方法的研究[J].军事进修学院学报,1994,15(2):124-126.
[10]Prabhakar G,Mehra K S,Ramamoorthy N,et al.Evaluation of radioiodination of meta-iodobenzylguanidine(MIBG)catalyzed by in situ generated Cu(I)and directly added Cu(II)[J].Appl Radiat Isot,1999,50(6):1011-1014.
[11]陈宝军,陈大明,杨红伟,等.123I-MIBG的制备及动物实验研究[J].原子能科学技术,2010,44(11):1299-1302.
[12]张锦明,田嘉禾,金小海,等.131I-间碘苄胍稳定性的研究[J].同位素,1996,9(4):219-222.