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

• Published in: BMC cancer Vol. 21; no. 1; pp. 348 - 13
• Main Authors: Huang, Yu-Sen, Chen, Jenny Ling-Yu, Chen, Hsin-Ming, Yeh, Li-Hao, Shih, Jin-Yuan, Yen, Ruoh-Fang, Chang, Yeun-Chung
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 01.04.2021; BioMed Central; BMC
• Subjects: Adult; Aged; Aged, 80 and over; Angiogenesis; Angiogenesis inhibitors; Angiogenin; Angiopoietin; Biomarkers; Cancer therapies; Carcinoma, Non-Small-Cell Lung - diagnostic imaging; Carcinoma, Non-Small-Cell Lung - mortality; Care and treatment; Clinical medicine; Cohort Studies; Deoxyribonucleic acid; Diagnosis; Diffusion coefficient; DNA; FDA approval; Female; Health aspects; Humans; Lung cancer; Lung cancer, Non-small cell; Lung Neoplasms - diagnostic imaging; Lung Neoplasms - mortality; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Male; Medical prognosis; Metabolism; Middle Aged; Mutation; Neovascularization; Non-small cell lung carcinoma; Patients; Permeability; Personalized medicine; PET imaging; Positron emission tomography; Positron-Emission Tomography - methods; Precision Medicine - methods; Prospective Studies; Radiologic biomarkers; Small cell lung carcinoma; Survival; Survival Analysis; Tomography; Tomography, X-Ray Computed - methods; Tumors; Vascular endothelial growth factor; Taiwan; United States > US; Germany; Angiogenesis inhibitors; Personalized medicine; Radiologic biomarkers; Survival
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-021-08064-4

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. 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 ), reverse reflux rate constant (k ), volume transfer constant (K ), blood plasma volume fraction (v ), extracellular extravascular volume fraction (v ), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC ). 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. 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 , and k , 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 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 (p = 0.046), K  > 200 10 /min (p = 0.069), and k  > 900 10 /min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival. 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.