Authors: | Kossatz, S.; Carney, B.; Schweitzer, M.; Carlucci, G.; Miloushev, V. Z.; Maachani, U. B.; Rajappa, P.; Keshari, K. R.; Pisapia, D.; Weber, W. A.; Souweidane, M. M.; Reiner, T. |
Article Title: | Biomarker-based PET imaging of diffuse intrinsic pontine glioma in mouse models |
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. © 2017 American Association for Cancer Research. |
Keywords: | controlled study; human tissue; protein expression; unclassified drug; histopathology; nonhuman; comparative study; neuroimaging; nuclear magnetic resonance imaging; positron emission tomography; diagnostic accuracy; sensitivity and specificity; biological marker; animal cell; mouse; animal tissue; computer assisted tomography; tumor volume; animal experiment; animal model; in vivo study; cancer infiltration; intermethod comparison; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor; tumor growth; fluorine 18; drug tumor level; mouse model; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase 1; diagnostic test accuracy study; pontine glioma; human; article; genetically engineered mouse strain; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase inhibitor f 18 |
Journal Title: | Cancer Research |
Volume: | 77 |
Issue: | 8 |
ISSN: | 0008-5472 |
Publisher: | American Association for Cancer Research |
Date Published: | 2017-04-15 |
Start Page: | 2112 |
End Page: | 2123 |
Language: | English |
DOI: | 10.1158/0008-5472.can-16-2850 |
PUBMED: | 28108511 |
PROVIDER: | scopus |
PMCID: | PMC5392368 |
DOI/URL: | |
Notes: | Article -- Export Date: 2 June 2017 -- Source: Scopus |