Assessing Tumor Angiogenesis Using Dynamic Contrast-Enhanced Integrated Magnetic Resonance-Positron Emission Tomography in Patients with Non-Small-cell Lung Cancer

BackgroundAngiogenesis 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.MethodsThis 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 (SUVmax), 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 60s 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.ResultsSerum 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>30cm(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.ConclusionsThe 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.