Synthesis and Evaluation of 111In-DOTA-mAb109 Monoclonal Antibody for Potential SPECT Molecular Imaging
Received date: 2014-12-02
Online published: 2014-12-11
Supported by
Project supported by the National Natural Science Foundation of China (Nos. 81172083, 81371592, 81401467) & Beijing Natural Science Foundation (Nos. 7132040, 81401467), the Seeding Grant for Medicine and Engineering Sciences of Peking University (2014-ME-12).
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 99mTc-labeled mAb109 for Single-photon emission computed tomography (SPECT) imaging. Those studies have showed that 99mTc-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-tetraazacyclododecane-1,4,7,10-tetraacetic acid-mAb 109 (DOTA-mAb109) was synthesized for potential radioactive imaging agents. Then, a radioisotope indium-111 (t1/2=67.3 h) was labeling to DOTA-mAb109 for further radio-biological evaluation. The DOTA is chelated to the 111In3＋ center through four nitrogens and four carboxylate oxygens, resulting in an eight-coordinate complex. The labeling efficiency of 111In-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 ℃. Less than 5% 111In dissociation was detected by Radio-HPLC. 111In-DOTA- mAb109 shows excellent radiochemical property. Nano-SPECT imaging of pancreatic carcinoma-1 tumor-bearing nude mice revealed that tumor uptake of 111In-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 111In-DOTA-mAb109. Uptake in the tumor was clearly visualized by emission computed tomography. These results suggest that the 111In-DOTA-mAb109 molecular probe is a promising tracer for tumor diagnosis.
Key words： mAb 109 molecular probe; tumor target; SPECT imaging; indium-111
Zhu Hua , Li Nan , Zhang Hong , Lin Xinfeng , Li Zhenfu , Yang Zhi . Synthesis and Evaluation of 111In-DOTA-mAb109 Monoclonal Antibody for Potential SPECT Molecular Imaging[J]. Acta Chimica Sinica, 2015 , 73(1) : 36 -40 . DOI: 10.6023/A14120832
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