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 DIPGin vivoIn 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.
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Susanne
authors.initials: S
authors.lastname: Kossatz
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Chemistry, Hunter College and PhD Program in Chemistry, The Graduate Center of the City University of New York, New York, New York.
authors.forename: Brandon
authors.initials: B
authors.lastname: Carney
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, New York.
authors.forename: Melanie
authors.initials: M
authors.lastname: Schweitzer
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Carlucci
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Vesselin Z
authors.initials: VZ
authors.lastname: Miloushev
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, New York.
authors.forename: Uday B
authors.initials: UB
authors.lastname: Maachani
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, New York.
authors.forename: Prajwal
authors.initials: P
authors.lastname: Rajappa
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Radiology, Weill Cornell Medical College, New York, New York.|Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Kayvan R
authors.initials: KR
authors.lastname: Keshari
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: David
authors.initials: D
authors.lastname: Pisapia
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.|Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Wolfgang A
authors.initials: WA
authors.lastname: Weber
authors.affiliation: Department of Neurological Surgery, Weill Cornell Medical College, New York, New York.|Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Souweidane
authors.affiliation: Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. reinert@mskcc.org.|Department of Radiology, Weill Cornell Medical College, New York, New York.
authors.forename: Thomas
authors.initials: T
authors.lastname: Reiner
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000096:biosynthesis; D020295:Brain Stem Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D002645:Chickens; D004195:Disease Models, Animal; D005557:Formaldehyde; D005910:Glioma / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D016612:Paraffin Embedding; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000032:analysis / Q000096:biosynthesis; D000072078:Positron Emission Tomography Computed Tomography / Q000379:methods; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals; D016707:Tissue Fixation
chemical_list: D014408:Biomarkers, Tumor; D019275:Radiopharmaceuticals; D005557:Formaldehyde; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1