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Optimal Saturated Neuropilin-1 Expression in Normal Tissue Maximizes Tumor Exposure to Anti-Neuropilin-1 Monoclonal Antibody

[ Vol. 19 , Issue. 18 ]

Author(s):

Chao Ma, Xiaofeng Dou, Jianghua Yan, Shengyu Wang, Rongshui Yang, Fu Su*, Huijuan Zhang* and Xinhui Su*   Pages 2269 - 2275 ( 7 )

Abstract:


Background: As involved in tumor angiogenesis, Neuropilin Receptor type-1 (NRP-1) serves as an attractive target for cancer molecular imaging and therapy. Widespread expression of NRP-1 in normal tissues may affect anti-NRP-1 antibody tumor uptake.

Objective: To assess a novel anti-NRP-1 monoclonal antibody A6-11-26 biodistribution in NRP-1 positive tumor xenograft models to understand the relationships between dose, normal tissue uptake and tumor uptake.

Methods: The A6-11-26 was radiolabeled with 131I and the mice bearing U87MG xenografts were then administered with 131I-labelled A6-11-26 along with 0, 2.5, 5, and 10mg·kg-1 unlabelled antibody A6-11-26. Biodistribution and SPECT/CT imaging were evaluated.

Results: 131I-A6-11-26 was synthesized successfully by hybridoma within 60min. It showed that most of 131IA6- 11-26 were in the plasma and serum (98.5 ± 0.16 and 88.9 ± 5.84, respectively), whereas, less in blood cells. For in vivo biodistribution studies, after only injection of 131I-A6-11-26, high levels of radioactivity were observed in the liver, moderate level in lungs. However, liver and lungs radioactivity uptakes could be competitively blocked by an increasing amount of unlabeled antibody A6-11-26, which can increase tumor radioactivity levels, but not in a dose-dependent manner. A dose between 10 and 20mg·kg-1 of unlabeled antibody A6-11-26 may be the optimal dose that maximized tumor exposure.

Conclusion: Widespread expression of NRP-1 in normal tissue may affect the distribution of A6-11-26 to tumor tissue. An appropriate antibody A6-11-26 dose would be required to saturate normal tissue antigenic sinks to achieve acceptable tumor exposure.

Keywords:

Neuropilin-1, monoclonal antibody, molecular therapy, cancer, angiogenesis, xenografts.

Affiliation:

Department of Nuclear Medicine, Zhongshan Hospital Xiamen University, Xiamen 361004, Department of Nuclear Medicine, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310052, Cancer Research Center of Medical School, Xiamen University, Xiamen 361102, Cancer Research Center of Medical School, Xiamen University, Xiamen 361102, Department of Nuclear Medicine, Zhongshan Hospital Xiamen University, Xiamen 361004, Department of Nuclear Medicine, Zhongshan Hospital Xiamen University, Xiamen 361004, Department of Radiology, Jinshan Branch, Fujian Provincial Hospital of Fujian Medical University, Fuzhou 350001, Department of Nuclear Medicine, Zhongshan Hospital Xiamen University, Xiamen 361004

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