99mTc-HisoDGR as a Potential SPECT Probe for Orthotopic Glioma Detection via Targeting of Integrin α5β1

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• 作者：Haitao Zhao ; Hannan Gao ; Luoping Zhai ; Xujie Liu ; Bing Jia ; Jiyun Shi ; Fan Wang
• 刊名：Bioconjugate Chemistry
• 出版年：2016
• 出版时间：May 18, 2016
• 年：2016
• 卷：27
• 期：5
• 页码：1259-1266
• 全文大小：490K
• 年卷期：0
• ISSN：1520-4812

文摘

Integrins, a large family of cell adhesion receptors, have been shown to play an important role for glioma proliferation and invasion. Several integrin receptors, including α_vβ₃, α_vβ₅, and α₅β₁, have generated clinical interest for glioma diagnosis and antitumor therapy. Integrin α₅β₁ has been highlighted as a prognostic and diagnostic marker in glioma, and its expression is correlated with a worse prognosis in high-grade glioma. However, unlike extensively studied integrins α_vβ₃ and α_vβ₅, very few integrin α₅β₁-specific radiotracers have been reported. Developing α₅β₁-specific radiotracers may provide alternative diagnosis and evaluation options in addition to well-studied α_vβ₃/α_vβ₅-specific tracers, and they may add new documents for profiling tumor progression. Here, a novel integrin α₅β₁-specific probe ^99mTc-HisoDGR was fabricated for SPECT (single-photon emission computed tomography) imaging of glioma. To confirm its selective targeting of integrin α₅β₁ in vivo, the mouse models of α₅β₁-positive U87MG human glioma were subjected to SPECT/CT scans, and biodistribution experiments and blocking studies were performed. Small-animal SPECT/CT imaging experiments demonstrated that the tumors were clearly visualized in both subcutaneous and orthotopic glioma tumor models with clear background at 0.5, 1, and 2 h p.i. The tumor accumulation of ^99mTc-HisoDGR showed significant reduction when excess cold isoDGR peptide was coinjected, suggesting that the tumor uptake was specifically mediated. Our work revealed that ^99mTc-HisoDGR represented a powerful molecular probe for integrin α₅β₁-positive cancer imaging; moreover, it might be a promising tool for evaluating malignancy, predicting prognosis, selecting subpopulations of patients who might be sensitive to integrin α₅β₁-targeted drugs, and assessing and monitoring the response to integrin α₅β₁-targeted drugs in clinical trials.