Multimodality Multiparametric Imaging of Early Tumor Response to a Novel Antiangiogenic Therapy Based on AnticalinsReportar como inadecuado




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Anticalins are a novel class of targeted protein therapeutics. The PEGylated Anticalin Angiocal PRS-050-PEG40 is directed against VEGF-A. The purpose of our study was to compare the performance of diffusion weighted imaging DWI, dynamic contrast enhanced magnetic resonance imaging DCE-MRI and positron emission tomography with the tracer 18Ffluorodeoxyglucose FDG-PET for monitoring early response to antiangiogenic therapy with PRS-050-PEG40. 31 mice were implanted subcutaneously with A673 rhabdomyosarcoma xenografts and underwent DWI, DCE-MRI and FDG-PET before and 2 days after i.p. injection of PRS-050-PEG40 n = 13, Avastin n = 6 or PBS n = 12. Tumor size was measured manually with a caliper. Imaging results were correlated with histopathology. In the results, the tumor size was not significantly different in the treatment groups when compared to the control group on day 2 after therapy onset P = 0.09. In contrast the imaging modalities DWI, DCE-MRI and FDG-PET showed significant differences between the therapeutic compared to the control group as early as 2 days after therapy onset P<0.001. There was a strong correlation of the early changes in DWI, DCE-MRI and FDG-PET at day 2 after therapy onset and the change in tumor size at the end of therapy r = −0.58, 0.71 and 0.67 respectively. The imaging results were confirmed by histopathology, showing early necrosis and necroptosis in the tumors. Thus multimodality multiparametric imaging was able to predict therapeutic success of PRS-050-PEG40 and Avastin as early as 2 days after onset of therapy and thus promising for monitoring early response of antiangiogenic therapy.



Autor: Reinhard Meier , Rickmer Braren, Yvonne Kosanke, Johanna Bussemer, Frauke Neff, Moritz Wildgruber, Sarah Schwarzenböck, Annette

Fuente: http://plos.srce.hr/



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