Specific Targeting of Human Integrin αvβ3 with 111In-Labeled Abegrin™ in Nude Mouse Models | springermedicine.com

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Molecular Imaging and Biology

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01-02-2011 | Research Article

Specific Targeting of Human Integrin α_vβ₃ with ¹¹¹In-Labeled Abegrin™ in Nude Mouse Models

Authors: Zhaofei Liu, Bing Jia, Huiyun Zhao, Xiaoyuan Chen, Fan Wang

Published in: Molecular Imaging and Biology | Issue 1/2011

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Abstract

Purpose

The cell adhesion molecule integrin α_vβ₃ is an important player in the process of tumor angiogenesis and metastasis. Abegrin™, a fully humanized anti-integrin α_vβ₃ monoclonal antibody, was currently in clinical trials for cancer therapy. Herein, we labeled Abegrin™ with ¹¹¹In, evaluated the in vitro and in vivo characteristics, and investigated whether the expression of integrin α_vβ₃ in tumors could be imaged with ¹¹¹In-labeled Abegrin™.

Methods

The binding affinity and specificity of Abegrin™ was analyzed using U87MG glioblastoma cells. Abegrin™ was coupled with 1,4,7,10-tetraazadodecane-N,N′,N″,N′″-tetraacetic acid (DOTA) for ¹¹¹In radiolabeling. γ Imaging of ¹¹¹In-DOTA–Abegrin™ was carried out in nude mice bearing both integrin α_vβ₃-positive U87MG and integrin α_vβ₃-negative HT-29 tumors. Biodistribution and blocking studies of ¹¹¹In-DOTA–Abegrin™ were investigated in U87MG tumor-bearing nude mice.

Results

Abegrin™ exhibited high-binding affinity to human integrin α_vβ₃ expressed on U87MG cells (K _d of 0.35 ± 0.06 nM). The antibody retained antigen-binding affinity/specificity after DOTA conjugation. γ Imaging showed that the tumor uptake of ¹¹¹In-DOTA–Abegrin™ in integrin α_vβ₃-positive U87MG tumors was much higher than that in integrin α_vβ₃-negative HT-29 tumors. In the HT-29 tumors, Abegrin™ was mainly nonspecifically accumulated around the blood vessels, while in the U87MG tumors, besides the nonspecific tumor retention, Abegrin™ also specifically bound the human integrin α_vβ₃ expressed on the tumor cells. Biodistribution and blocking studies exhibited that the U87MG tumor uptake of ¹¹¹In-DOTA–Abegrin™ decreased from 14.12 ± 0.44 to 6.93 ± 0.94 percentage of injected dose per gram of tissue after coinjection of excess dose of cold Abegrin™, which confirmed the in vivo integrin α_vβ₃ binding specificity of ¹¹¹In-DOTA–Abegrin™.

Conclusions

Abegrin™ showed specific binding to human integrin α_vβ₃ expressed on the tumor cells. ¹¹¹In-DOTA–Abegrin™ can specifically target the human integrin α_vβ₃ expression in the nude mouse model. ¹¹¹In-DOTA–Abegrin™ has a potential for clinical translation as an agent for integrin α_vβ₃-positive tumor imaging, evaluating tumor angiogenic status and monitoring the therapeutic efficacy of Abegrin™-based cancer therapy.

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Title: Specific Targeting of Human Integrin αvβ3 with 111In-Labeled Abegrin™ in Nude Mouse Models
Authors: Zhaofei Liu
Bing Jia
Huiyun Zhao
Xiaoyuan Chen
Fan Wang
Publication date: 01-02-2011
Publisher: Springer-Verlag
Published in: Molecular Imaging and Biology / Issue 1/2011
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI: https://doi.org/10.1007/s11307-010-0302-4

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