Biomarker-Based PET Imaging of Diffuse Intrinsic Pontine Glioma in Mouse Models

Cancer Res. 2017 Apr 15;77(8):2112-2123. doi: 10.1158/0008-5472.CAN-16-2850. Epub 2017 Jan 20.

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a universally poor prognosis. Here, we characterize a positron emission tomography (PET) probe for imaging DIPG in vivo In human histological tissues, the probes target, PARP1, was highly expressed in DIPG compared to normal brain. PET imaging allowed for the sensitive detection of DIPG in a genetically engineered mouse model, and probe uptake correlated to histologically determined tumor infiltration. Imaging with the sister fluorescence agent revealed that uptake was confined to proliferating, PARP1-expressing cells. Comparison with other imaging technologies revealed remarkable accuracy of our biomarker approach. We subsequently demonstrated that serial imaging of DIPG in mouse models enables monitoring of tumor growth, as shown in modeling of tumor progression. Overall, this validated method for quantifying DIPG burden would serve useful in monitoring treatment response in early phase clinical trials. Cancer Res; 77(8); 2112-23. ©2017 AACR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / biosynthesis
  • Brain Stem Neoplasms / diagnostic imaging*
  • Brain Stem Neoplasms / metabolism
  • Brain Stem Neoplasms / pathology
  • Chickens
  • Disease Models, Animal
  • Formaldehyde
  • Glioma / diagnostic imaging*
  • Glioma / metabolism
  • Glioma / pathology
  • Humans
  • Magnetic Resonance Imaging / methods
  • Mice
  • Paraffin Embedding
  • Poly (ADP-Ribose) Polymerase-1 / analysis
  • Poly (ADP-Ribose) Polymerase-1 / biosynthesis
  • Positron Emission Tomography Computed Tomography / methods
  • Positron-Emission Tomography / methods*
  • Radiopharmaceuticals
  • Tissue Fixation

Substances

  • Biomarkers, Tumor
  • Radiopharmaceuticals
  • Formaldehyde
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1