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

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 alpha(v)beta(3), alpha(v)beta(5), and alpha(5)beta(1), have generated clinical interest for glioma diagnosis and antitumor therapy. Integrin alpha(5)beta(1) 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 alpha(v)beta(3) and alpha(v)beta(5), very few integrin alpha(5)beta(1)-specific radiotracers have been reported. Developing alpha(5)beta(1)-specific radiotracers may provide alternative diagnosis and evaluation options in addition to well-studied alpha(v)beta(3)/alpha(v)beta(5)-specific tracers, and they may add new documents for profiling tumor progression. Here, a novel integrin alpha(5)beta(1)-specific probe Tc-99m-HisoDGR was fabricated for SPECT (single-photon emission computed tomography) imaging of glioma. To confirm its selective targeting of integrin alpha(5)beta(1) in vivo, the mouse models of alpha(5)beta(1)-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 Tc-99m-HisoDGR showed significant reduction when excess cold isoDGR peptide was coinjected, suggesting that the tumor uptake was specifically mediated. Our work revealed that Tc-99m-HisoDGR represented a powerful molecular probe for integrin alpha(5)beta(1)-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 alpha(5)beta(1)-targeted drugs, and assessing and monitoring the response to integrin alpha(5)beta(1)-targeted drugs in clinical trials.