Earlier Detection of Breast Cancer with Ultrasound Molecular Imaging in a Transgenic Mouse Model
Menée à l'aide d'un modèle murin transgénique, cette étude évalue les performances d'une technique d'imagerie acoustique à base de microbulles ciblées sur le récepteur VEGFR2 pour la détection précoce d'un cancer du sein
While there is an increasing role of ultrasound for breast cancer screening in patients with dense breast, conventional anatomical-ultrasound lacks sensitivity and specificity for early breast cancer detection. In this study we assessed the potential of molecular-ultrasound imaging, using clinically-translatable vascular endothelial growth factor receptor (VEGFR2)-targeted microbubbles (MBVEGFR2), to improve the diagnostic accuracy of ultrasound in earlier detection of breast cancer and ductal carcinoma in situ (DCIS) in a transgenic mouse model (FVB/N-Tg(MMTV-PyMT)634Mul). In vivo binding specificity studies (n=26 tumors) showed that ultrasound imaging signal was significantly higher (P<0.001) using MBVEGFR2 compared to non-targeted microbubbles and imaging signal significantly decreased (P<0.001) by blocking antibodies. Ultrasound molecular imaging signal significantly increased (P<0.001), when breast tissue (n=315 glands) progressed from normal (1.65±0.17 a.u.) to hyperplasia (4.21±1.16), DCIS (15.95±1.31) and invasive cancer (78.1±6.31) and highly correlated with ex vivo VEGFR2 expression (R2=0.84; 95% CI, 0.72, 0.91; P<0.001). At an imaging signal threshold of 4.6 a.u., ultrasound molecular imaging differentiated benign from malignant entities with a sensitivity of 84% (95% CI, 78, 88) and specificity of 89% (95% CI, 81, 94). In a prospective screening trail (n=63 glands) diagnostic performance of detecting DCIS and breast cancer was assessed and two independent readers correctly diagnosed malignant disease in >95% of cases and highly agreed between each other (ICC=0.98; 95% CI, 97, 99). These results suggest that VEGFR2-targeted ultrasound molecular imaging allows highly accurate detection of DCIS and breast cancer in transgenic mice and may be a promising approach for early breast cancer detection in women.
Cancer Research , résumé, 2013