4.8 Article

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

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CANCER RESEARCH
卷 77, 期 8, 页码 2112-2123

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AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-16-2850

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  1. National Institutes of Health [NIH1 R01 HL125703, R01CA204441, R21CA191679, K25 EB016673, P30 CA008748-50]
  2. Center for Molecular Imaging and Nanotechnology (CMINT)
  3. Tow Fellowship Program in Molecular Imaging and Nanotechnology
  4. MSKCC Radiology Development Project Grant
  5. National Science Foundation [IGERT 0965983]
  6. German Research Foundation

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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. (C) 2017 AACR.

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