Assessing tumor angiogenesis using dynamic contrast-enhanced integrated magnetic resonance-positron emission tomography in patients with non-small-cell lung cancer

Background Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC. Methods This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUV max ), reverse reflux rate constant ( k ep ), volume transfer constant ( K trans ), blood plasma volume fraction ( v p ), extracellular extravascular volume fraction ( v e ), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC 60 ). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously. Results Serum VEGF-A ( p = 0.002), angiogenin ( p = 0.023), and Ang-1 ( p < 0.001) concentrations were significantly elevated in NSCLC patients compared with healthy individuals. MR-PET parameters, including MTV, K trans , and k ep , showed strong linear correlations ( p < 0.001) with serum angiogenesis-related biomarkers. Serum VEGF-A concentrations ( p = 0.004), MTV values ( p < 0.001), and k ep values ( p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm 3 ( p = 0.046), K trans > 200 10 − 3 /min ( p = 0.069), and k ep > 900 10 − 3 /min ( p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival. Conclusions The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.