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Synthesis and Evaluation of In-111-DOTA-mAb109 Monoclonal Antibody for Potential SPECT Molecular Imaging
Zhu Hua1; Li Nan1; Zhang Hong2; Lin Xinfeng1; Li Zhenfu2; Yang Zhi1
关键词Mab 109 Molecular Probe Tumor Target Spect Imaging Indium-111
刊名ACTA CHIMICA SINICA
2015-01-15
DOI10.6023/A14120832
73期:1页:36-40
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Chemistry, Multidisciplinary
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Seeding Grant for Medicine and Engineering Sciences of Peking University ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Seeding Grant for Medicine and Engineering Sciences of Peking University
研究领域[WOS]Chemistry
关键词[WOS]CANCER
英文摘要

Peroxiredoxin-I is a protein encoded by the Peroxiredoxin I gene, which highly expressed in many tumor tissues, such as lung cancer, breast cancer, rectal cancer, stomach cancer. Peroxiredoxin-I has a proliferative effect and plays a role in cancer development, recurrence or progression. The mAb 109 antibody can specific binding to Peroxiredoxin-I protein. We recently reported the synthesis Tc-99m-labeled mAb109 for Single-photon emission computed tomography (SPECT) imaging. Those studies have showed that Tc-99m-mAb 109 still preserved its biological functions and specifically binding to the target tumors. The aim of this research was to develop new radionuclide labeled mAb109 antibody for prolonged tumor targeted molecular imaging. In this paper, the precursor compound 2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane1,4,7,10-tetraacetic acid-mAb 109 (DOTA-mAb109) was synthesized for potential radioactive imaging agents. Then, a radioisotope indium-111 (t(1/2)= 67.3 h) was labeling to DOTA-mAb109 for further radio-biological evaluation. The DOTA is chelated to the In-111(3+) center through four nitrogens and four carboxylate oxygens, resulting in an eight-coordinate complex. The labeling efficiency of In-111-DOTA-mAb109 was tested by Radio-TLC/HPLC. The radiolabeling yield was over 96%, the radio chemical purity was over 99% by PD-10 column purification. The in vitro stability tests were presented in 5% Human serum albumin (HSA) for 72 h at 25 degrees C Less than 5% In-111 dissociation was detected by Radio-HPLC. In-111-DOTA-mAb109 shows excellent radiochemical property. Nano-SPECT imaging of pancreatic carcinoma-1 tumor-bearing nude mice revealed that tumor uptake of In-111-DOTA-mAb109 got a gradual accumulation from 24 h, 48 h to 72 h after post-injection of 18.5 MBq radiolabeled antibody. The cardiac area was clearly seen up to 48 h post injection, reflecting a long blood circulation time for In-111-DOTA-mAb109. Uptake in the tumor was clearly visualized by emission computed tomography. These results suggest that the In-111-DOTA-mAb109 molecular probe is a promising tracer for tumor diagnosis.

语种中文
所属项目编号81172083 ; 81371592 ; 81401467 ; 81401467 ; 7132040 ; 2014-ME-12
资助者National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Seeding Grant for Medicine and Engineering Sciences of Peking University ; National Natural Science Foundation of China ; Beijing Natural Science Foundation ; Seeding Grant for Medicine and Engineering Sciences of Peking University
WOS记录号WOS:000348595200004
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/55861
专题北京大学临床肿瘤学院_核医学科
作者单位1.Peking Univ, Canc Hosp & Inst, Key Lab Carcinogenesis & Translat Res, Minist Educ, Beijing 100142, Peoples R China
2.Peking Univ, Canc Hosp & Inst, Dept Nucl Med, Cent Lab, Beijing 100142, Peoples R China
推荐引用方式
GB/T 7714
Zhu Hua,Li Nan,Zhang Hong,et al. Synthesis and Evaluation of In-111-DOTA-mAb109 Monoclonal Antibody for Potential SPECT Molecular Imaging[J]. ACTA CHIMICA SINICA,2015,73(1):36-40.
APA Zhu Hua,Li Nan,Zhang Hong,Lin Xinfeng,Li Zhenfu,&Yang Zhi.(2015).Synthesis and Evaluation of In-111-DOTA-mAb109 Monoclonal Antibody for Potential SPECT Molecular Imaging.ACTA CHIMICA SINICA,73(1),36-40.
MLA Zhu Hua,et al."Synthesis and Evaluation of In-111-DOTA-mAb109 Monoclonal Antibody for Potential SPECT Molecular Imaging".ACTA CHIMICA SINICA 73.1(2015):36-40.
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