177Lu标记单克隆抗体Rituximab

doi:10.7538/tws.2014.27.02.0098

摘要/Abstract

摘要：

以CHX-A''-DTPA和p-SCN-Bz-DTPA为双功能螯合剂，分别对Rituximab进行偶联，用¹⁷⁷Lu进行标记，制备¹⁷⁷Lu-Rituximab。在优化条件下，¹⁷⁷Lu对单抗偶联物CHX-A''-DTPA-Rituximab和p-SCN-Bz-DTPA-Rituximab的标记率和放化纯度均大于99%。室温及37 ℃条件下，¹⁷⁷Lu-Rituximab在各种测试体系中均显示良好的体外稳定性。在正常小鼠体内的生物分布结果显示，¹⁷⁷Lu-Rituximab发生了分解，游离的¹⁷⁷Lu在骨中形成较高浓集。¹⁷⁷Lu-p-SCN-Bz-DTPA-Rituximab比¹⁷⁷Lu-CHX-A''-DTPA-Rituximab的体内清除快，而且游离¹⁷⁷Lu的骨摄取低，结果表明，p-SCN-Bz-DTPA更适于作为双功能螯合剂用于单抗的¹⁷⁷Lu 标记。

关键词: Rituximab, 双功能螯合剂, ¹⁷⁷Lu, 生物分布

Abstract:

For evaluating whether ¹⁷⁷Lu-Rituximab could be applied for radioimmunoimaging and radioimmunotherrapy of non-Hodgkin’s Lymphoma， Rituximab, a specific chimeric monoclonal antibody used in CD20-positive B-cell Non-Hodgkin’s Lymphoma, was conjugated to bifunctional chelating agents (CHX-A''-DTPA and p-SCN-Bz-DTPA) and radiolabelled with ¹⁷⁷Lu successively. ¹⁷⁷Lu-CHX-A''-DTPA-Rituximab and ¹⁷⁷Lu-p-SCN-Bz-DTPA-Rituximab were obtained with labelling yield and radiochemical purity higher than 99% at optimized conditions, and showed good in vitro stability in different testing system at room temperature and 37 ℃. However, the results of biodistribution in normal mice showed high uptakes in bone which indicated that ¹⁷⁷Lu released from the radiolabelled antibodies. The retention of free ¹⁷⁷Lu in the bone was lower for ¹⁷⁷Lu-p-SCN-Bz-DTPA-Rituximab compared with ¹⁷⁷Lu-CHX-A''-DTPA-Rituximab. Our preliminary work demonstrated that p-SCN-Bz-DTPA may be more suitable for ¹⁷⁷Lu labelling of monoclonal antibodies.

Key words: Rituximab, bifunctional chelating agent, ¹⁷⁷Lu, biodistribution

马秀凤;张君丽;李洪玉;梁积新;杨云;杨春慧;杜进. ¹⁷⁷Lu标记单克隆抗体Rituximab[J]. 同位素, 2014, 27(2): 98-103.

MA Xiu-feng1;ZHANG Jun-li2;LI Hong-yu;LIANG Ji-xin;YANG Yun2;YANG Chun-hui2;DU Jin1,3 . Preparation and Preliminary Biological Evaluation of ¹⁷⁷Lu Labelled Rituximab[J]. Journal of Isotopes, 2014, 27(2): 98-103.

参考文献

[1]Robak T, Robak P, Smolewski P. The evaluation and optimal use of rituximab in lymphoid malignancies[J]. Blood and Lymphatic Cancer: Targets and Therapy 2012, 2: 1-16.
[2]Juweid ME. Radioimmunotherapy of B-Cell Non-Hodgkin’s Lymphoma: From Clinical Trials to Clinical Practice[J]. J Nucl Med 2002, 43: 1507-1529.
[3]McLaughlin P. Rituximab: perspective on single agent experience and future directions in combination trials[J]. Critical Reviews in Oncology/Hematology 2001, 40: 3-16.
[4]Jazirehi AR, Bonavida B. Cellular and molecular signal transduction pathways modulated by rituximab (rituxan,anti-CD20-mAb) in non-Hodgkin’s lymphoma:implications in chemosensitization and therapeutic intervention[J]. Oncogene 2005, 24: 2121-2143.
[5]Bernhardt P, Forssell-Aronsson E, Jacobsson L, et al. Low-energy electron emitters for targeted radiotherapy of small tumours[J]. Acta Oncol 2001, 40: 602-608.
[6]Bernhardt P, Benjegard SA, Kolby L, et al. Dosimetric comparison of radionuclides for therapy of somatostatin receptor-expressing tumors[J]. Int J Radiat Oncol Biol Phys 2001, 51: 514-524.
[7]Tapas D, M.R.A. P. Options to meet the future global demand of radionuclides for radionuclide therapy[J]. Nucl Med Biol 2013, 40: 23-32.
[8]Reilly RM. Monoclonal Antibody and Peptide-Targeted Radiotherapy of Cancer[M]. New Jersey: John Wiley & Sons,Inc, 2010.
[9]S Liu, Edwards DS. Bifunctional Chelators for Therapeutic Lanthanide Radiopharmaceuticals[J]. Bioconjugate Chem 2001, 12:7-34．
[10]Woods M, Kovacs Z, Sherry AD. Targeted Complexes of Lanthanide(III) Ions as Therapeutic and Diagnostic Pharmaceuticals[J]. J Sup Chem 2002, 2: 1-15.
[11]Hnatowich DJ, Childs RL, Lantelxne D, et al. DTPA-coupled Antibodies Labled with Yttrium-90[J]. J Nucl Med 1985, 26: 503.
[12]Müller WA, Linzner U, Sch ffer EH. Organ Distribution Studies of Lutetium-177 in Mouse[J]. Int J Nucl Med Biol 1978, 5:29-31.

[1]	马晶鑫;伍洲;姜申德;王红亮;武志芳. 肿瘤PET分子探针3-O-(2-¹⁸F-氟乙基)-L-多巴的合成及初步生物学评价[J]. 同位素, 2018, 31(5): 310-317.
[2]	黄钱焕;潘栋辉;徐宇平;盛洁;王彦婷;杨敏. ⁶⁸Ge/⁶⁸Ga发生器的临床应用[J]. 同位素, 2017, 30(4): 270-275.
[3]	李彦鹏;温馨;程兵;谢新立;杜晓光;韩星敏. (N-［¹⁸F］氟甲基)-胆碱的自动化合成及其生物分布研究[J]. 同位素, 2017, 30(1): 29-35.
[4]	王蕾;张晓军;周艳丽;张锦明. ¹⁸F-FDG-(OAc)₄在¹⁸F-FDG中的残留及在小鼠体内的生物分布[J]. 同位素, 2017, 30(1): 36-42.
[5]	李凤林;罗志福;樊彩云;刘子华;邓新荣. 巯基十二硼烷二钠盐的急性毒性与药代动力学研究[J]. 同位素, 2016, 29(3): 164-169.
[6]	雷晓;朱晓霞;王德才;孟志云;甘慧;顾若兰;吴卓娜;郑颖;李俭;吕明;窦桂芳. ¹²⁵I-MIL50在大鼠体内的药代动力学及生物分布[J]. 同位素, 2016, 29(2): 65-70.
[7]	韩振义;梁积新;胡骥;罗洪义;卿晶;陈玉清;李光;李洪玉. ⁶⁴Cu标记两种奥曲肽类似物的比较[J]. 同位素, 2016, 29(2): 82-88.
[8]	马欢;唐禹;杨远友;刘宁;廖家莉;杨吉军. ¹³¹I标记新型小分子肽VP2[J]. 同位素, 2016, 29(1): 1-5.
[9]	罗洪义;沈浪涛;梁积新;杨春慧;张文辉;秦少鹏;卫成军;刘海春;王建华;李洪玉. ^99mTc-帕米膦酸盐的制备及骨分布[J]. 同位素, 2016, 29(1): 6-11.
[10]	彭程;崔孟超;梁志刚;刘亭廷;张晓阳. ¹²⁵I标记的二噻吩查尔酮类Aβ斑块显像剂的制备与生物评价[J]. 同位素, 2015, 28(4): 253-258.
[11]	张锦明;张晓军;黄德晖;王卉;刘健;田嘉禾. 多发性硬化症显像剂¹¹C-CIC的合成[J]. 同位素, 2015, 28(4): 259-264.
[12]	李贵平;黄宝丹;杜丽;韩彦江;张辉;黄凯;郑文莉. 新型肺癌小分子多肽的¹³¹I标记及其在小鼠体内的生物分布[J]. 同位素, 2014, 27(2): 104-108.
[13]	李凤林;罗志福;邓新荣;樊彩云;刘子华;吴猛. 分光光度法测量生物组织中BPA含量[J]. 同位素, 2013, 26(3): 163-169.
[14]	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.
[15]	邓新荣 ;向学琴 ;李凤林 ;樊彩云 ;刘子华 ;陈阳 ;罗志福 . ¹⁷⁷Lu-DOTMP在荷瘤小鼠体内的生物分布和兔SPECT显像研究[J]. 同位素, 2012, 25(3): 160-164.

¹⁷⁷Lu标记单克隆抗体Rituximab

Preparation and Preliminary Biological Evaluation of ¹⁷⁷Lu Labelled Rituximab

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics