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

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

Diffuse intrinsic pontine glioma (DIPG) is a childhood brainstem tumor with a universally poor prognosis. Here, we characterize on a positron emission tomography (PET) probe for imaging DIPG in vivo. In human histological tissues, the probes target, poly(ADP)ribose polymerase 1 (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 (GEMM), 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 to 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.

Publication Name: 
Cancer Research
Authors: 
Kossatz S, Carney B, Schweitzer ME, Carlucci G, Miloushev V, Maachani UB, Rajappa P, Keshari K, Pisapia DJ, Weber WA, Souweidane MM, Reiner T

 

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