UNLABELLED: Epidermal growth factor receptor (EGFR) expression is upregulated in many types of tumors, and the EGFR tyrosine kinase inhibitor gefitinib has high potential as an anticancer drug. However, accumulating clinical evidence has indicated that only a subset of patients benefit from gefitinib treatment. This study aimed to determine whether optical imaging of vascular endothelial growth factor (VEGF) expression can be an early biomarker for tumor response to gefitinib therapy. METHODS: A VEGF-targeting fluorescent probe Dye-BevF(ab')2 was prepared and tested in vivo. Longitudinal optical imaging studies using Dye-BevF(ab')2 were performed in both 22B (gefitinib-resistant) and A549 (gefitinib-responsive) tumor models at different times (days 0, 2, and 5) before and after gefitinib treatment. The imaging results were validated by ex vivo immunofluorescence staining and enzyme-linked immunosorbent assay. RESULTS: Dye-BevF(ab')2 exhibited high specificity for VEGF in vivo. There was no significant change in the Dye-BevF(ab')2 uptake in gefitinib-treated 22B tumors, compared with the control group. In contrast, the A549 tumor uptake of Dye-BevF(ab')2 in the gefitinib-treated group was significantly lower on days 2 and 5 than that in the control group and at the baseline. An in vivo gefitinib treatment study confirmed that 22B tumors were gefitinib-resistant, whereas A549 tumors were gefitinib-responsive. Immunofluorescence staining and enzyme-linked immunosorbent assay confirmed that changes in the Dye-BevF(ab')2 uptake were correlated with VEGF expression levels in tumors. CONCLUSION: Optical imaging of VEGF expression with Dye-BevF(ab')2 can be used for the early assessment of tumor response to gefitinib therapy. This approach may also be valuable for preclinical high-throughput screening of novel antiangiogenic drugs.
UNLABELLED: Epidermal growth factor receptor (EGFR) expression is upregulated in many types of tumors, and the EGFR tyrosine kinase inhibitor gefitinib has high potential as an anticancer drug. However, accumulating clinical evidence has indicated that only a subset of patients benefit from gefitinib treatment. This study aimed to determine whether optical imaging of vascular endothelial growth factor (VEGF) expression can be an early biomarker for tumor response to gefitinib therapy. METHODS: A VEGF-targeting fluorescent probe Dye-BevF(ab')2 was prepared and tested in vivo. Longitudinal optical imaging studies using Dye-BevF(ab')2 were performed in both 22B (gefitinib-resistant) and A549 (gefitinib-responsive) tumor models at different times (days 0, 2, and 5) before and after gefitinib treatment. The imaging results were validated by ex vivo immunofluorescence staining and enzyme-linked immunosorbent assay. RESULTS: Dye-BevF(ab')2 exhibited high specificity for VEGF in vivo. There was no significant change in the Dye-BevF(ab')2 uptake in gefitinib-treated 22B tumors, compared with the control group. In contrast, the A549 tumor uptake of Dye-BevF(ab')2 in the gefitinib-treated group was significantly lower on days 2 and 5 than that in the control group and at the baseline. An in vivo gefitinib treatment study confirmed that 22B tumors were gefitinib-resistant, whereas A549 tumors were gefitinib-responsive. Immunofluorescence staining and enzyme-linked immunosorbent assay confirmed that changes in the Dye-BevF(ab')2 uptake were correlated with VEGF expression levels in tumors. CONCLUSION: Optical imaging of VEGF expression with Dye-BevF(ab')2 can be used for the early assessment of tumor response to gefitinib therapy. This approach may also be valuable for preclinical high-throughput screening of novel antiangiogenic drugs.
Authors: Rami S Kantar; Ghazal Lashgari; Elie I Tabet; Grant K Lewandrowski; Litia A Carvalho; Bakhos A Tannous Journal: Sci Rep Date: 2016-05-20 Impact factor: 4.379