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

TitleBiomarker-Based PET Imaging of Diffuse Intrinsic Pontine Glioma in Mouse Models.
Publication TypeJournal Article
Year of Publication2017
AuthorsKossatz S, Carney B, Schweitzer M, Carlucci G, Miloushev VZ, Maachani UB, Rajappa P, Keshari KR, Pisapia D, Weber WA, Souweidane MM, Reiner T
JournalCancer Res
Volume77
Issue8
Pagination2112-2123
Date Published2017 04 15
ISSN1538-7445
KeywordsAnimals, Biomarkers, Tumor, Brain Stem Neoplasms, Chickens, Disease Models, Animal, Formaldehyde, Glioma, Humans, Magnetic Resonance Imaging, Mice, Paraffin Embedding, Poly (ADP-Ribose) Polymerase-1, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Radiopharmaceuticals, Tissue Fixation
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 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. .

DOI10.1158/0008-5472.CAN-16-2850
Alternate JournalCancer Res
PubMed ID28108511
PubMed Central IDPMC5392368
Grant ListR01 HL125703 / HL / NHLBI NIH HHS / United States
R21 CA191679 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
K25 EB016673 / EB / NIBIB NIH HHS / United States
R01 CA204441 / CA / NCI NIH HHS / United States