Multimodality multiparametric imaging of early tumor response to a novel antiangiogenic therapy based on anticalins

PLoS One. 2014 May 6;9(5):e94972. doi: 10.1371/journal.pone.0094972. eCollection 2014.

Abstract

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 [18F]fluorodeoxyglucose (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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Bevacizumab
  • Female
  • Fluorodeoxyglucose F18
  • Lipocalins / therapeutic use*
  • Magnetic Resonance Imaging
  • Mice
  • Multimodal Imaging*
  • Neovascularization, Pathologic / diagnosis
  • Neovascularization, Pathologic / diagnostic imaging
  • Neovascularization, Pathologic / drug therapy*
  • Positron-Emission Tomography
  • Radiopharmaceuticals

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Lipocalins
  • Radiopharmaceuticals
  • angiocal protein
  • Fluorodeoxyglucose F18
  • Bevacizumab

Grant support

This work was supported by a grant from Pieris AG by the German Research Foundation (DFG) within the SFB-Initiative 824 (collaborative research center) “Imaging for Selection, Monitoring and Individualization of Cancer Therapies” (ISMIC, projects C5 and C6) and by the German Research Foundation (DFG) and the Technische Universität München within the funding programme Open Access Publishing. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.