Binding of αvβ3 Integrin-Specific Radiotracers Is Modulated by Both Integrin Expression Level and Activation Status

• DOI: 10.1007/s11307-017-1100-z
• Publication Date: 2017-07-10T10:08:48Z
• Authors: Alexandra Andriu; Julie Crockett; Sergio Dall’Angelo; Monica Piras; Matteo Zanda; Ian N. Fleming
• Keywords: 0301 basic medicine; 330; αvβ3 integrin; Cell Membrane; PET imaging; R; R Medicine; Integrin alphaVbeta3; Vascular Endothelial Growth Factor Receptor-2; 3. Good health; Integrin signalling; 03 medical and health sciences; src-Family Kinases; SDG 3 - Good Health and Well-being; Response assessment; Cell Line, Tumor; Humans; Radiopharmaceuticals; Extracellular Signal-Regulated MAP Kinases; Tumour angiogenesis; Radiolabelled RGD peptides; Research Article; Protein Binding

Molecular imaging of αvβ3 integrin has exhibited real potential to guide the appropriate use anti-angiogenic therapies. However, an incomplete understanding factors that influence binding integrin-specific radiotracers currently limits their for assessing response therapy in cancer patients. This study identifies two fundamental modulate uptake these radiotracers. Procedures Experiments were performed prostate (PC3) and glioblastoma (U87MG) cells, which differentially express integrin. used investigate effect manipulating expression or activation cellular assays. β3 measured by western blotting flow cytometry, respectively. The select pharmacological inhibitors on was also determined. Radiotracer proportional when it decreased (β3 knock-down cells) increased, either using cell signalling culturing cells different times. Studies with both small molecule arginine–glycine–aspartic acid (RGD)-based revealed increased radiotracer after Mn2+ talin head domain. Moreover, inhibition pathways (mitogen-activated protein kinase (MEK), Src VEGFR2) binding, reflecting reduced activity. Binding ligands radiolabelled RGD peptides is modulated status can provide otherwise inaccessible information significant implications therapies clinical studies.