Imaging and biodistribution of 131I labeled anti-neuropilin-2 monoclonal antibody in lung adenocarcinoma-bearing mice
10.3760/cma.j.issn.2095-2848.2018.01.009
- VernacularTitle:131I标记抗神经纤毛蛋白-2单克隆抗体在荷肺腺癌裸鼠中的生物分布及显像
- Author:
Lichun CHEN
1
;
Liangliang WANG
;
Xinhui SU
;
Jianghua YAN
;
Chao MA
;
Guoqiang CHEN
;
Shengyou CHEN
Author Information
1. 361004,厦门大学附属中山医院核医学科
- Keywords:
Neuropilin-2;
Antibodies,monoclonal;
Isotope labeling;
Iodine radioisotopes;
Radionuclide imaging;
Lung neoplasms;
Mice,nude
- From:
Chinese Journal of Nuclear Medicine and Molecular Imaging
2018;38(1):37-41
- CountryChina
- Language:Chinese
-
Abstract:
Objective To prepare 131I-anti-neuropilin-2-monoclonal antibody (131I-anti-NRP-2-mAb),and investigate its biodistribution and imaging in nude mice bearing xenografted lung adenocarcinoma,in order to evaluate its feasibility as an imaging agent targeting to NRP-2 positive tumors.Methods (1)131I-anti-NRP-2-mAb was prepared by Chloramine-T method under the optimum labeling conditions,then the labeling efficiency,radiochemical purity and stability were determined in vitro.(2) The binding fraction and receptor binding affinity of 131I-anti-NRP-2-mAb were measured in A549 human lung cancer cells by cell uptaking and binding experiments.(3) The A549 tumor-bearing mice were randomly divided into 4 groups with direct sampling method and were sacrificed at 6,24,48,and 72 h,respectively,after tail intravenous injection of 0.37 MBq 131I-anti-NRP-2-mAb.The distribution was measured,and the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were calculated.(4) Gamma imaging was performed in 6 mice,including 3 in the competitive inhibition control group (injected with 3.7 MBq 131I-anti-NRP-2-mAb and 100 μg atniNRP-2-mAb),at 6,24,48,and 72 h post-injection to observe the radioactivity in tumor.Two-sample t test was used for data analysis.Results (1) The labeling yield and radiochemical purity of 131I-anti-NRP-2-mAb were (94.69 ± 3.63) ％ and (98.56± 0.48) ％,respectively.The radiochemical purity was more than 85％ after incubating in phosphate-buffered solution at room temperature for 72 h.(2) At 60,120,180 and 240 min post-injection,the binding ratios of 131I-anti-NRP-2-mAb in A549 cells were (3.95±0.18)％,(5.19±0.65) ％,(6.60± 0.36) ％ and (5.58± 0.63) ％,respectively.When excessive anti-NRP-2-mAb were added,the binding ratios were reduced to (0.94±0.31)％,(1.12±0.17)％,(1.24±0.25)％ and (1.04±0.18) ％,respectively,which were significantly lower than those of non-inhibited group (t values:9.89-19.66,all P＜0.05).131I-anti-NRP-2-mAb bound to NRP-2 with high affinity half maximal inhibitory concentration (IC50 =(410.8±1.2) nmol/L).(3) Biodistribution study demonstrated that the T/M and T/B ratios increased with the time extension and were 3.83±0.18 and 1.10±0.20,respectively,at 72 h post-injection.(4) Gamma imaging studies revealed that 131I-anti-NRP-2-mAb could clearly identify A549 tumors 6 h post-injection,especially at 48 h post-injection.Tumors were not observed clearly in competitive inhibition control group.Conclusion 131I-anti-NRP-2-mAb has been successfully prepared,and it could target to NRP-2 specifically.
