Biomarker-based PET imaging of diffuse intrinsic pontine glioma in mouse models

Susanne Kossatz; Brandon Carney; Melanie Schweitzer; Giuseppe Carlucci; Vesselin Z. Miloushev; Uday B. Maachani; Prajwal Rajappa; Kayvan R. Keshari; David Pisapia; Wolfgang A. Weber; Mark M. Souweidane; Thomas Reiner

doi:10.1158/0008-5472.CAN-16-2850

Biomarker-based PET imaging of diffuse intrinsic pontine glioma in mouse models

Susanne Kossatz, Brandon Carney, Melanie Schweitzer, Giuseppe Carlucci, Vesselin Z. Miloushev, Uday B. Maachani, Prajwal Rajappa, Kayvan R. Keshari, David Pisapia, Wolfgang A. Weber, Mark M. Souweidane, Thomas Reiner

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

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.

Original language	English
Pages (from-to)	2112-2123
Number of pages	12
Journal	Cancer Research
Volume	77
Issue number	8
DOIs	https://doi.org/10.1158/0008-5472.CAN-16-2850
State	Published - 15 Apr 2017
Externally published	Yes

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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.",

author = "Susanne Kossatz and Brandon Carney and Melanie Schweitzer and Giuseppe Carlucci and Miloushev, {Vesselin Z.} and Maachani, {Uday B.} and Prajwal Rajappa and Keshari, {Kayvan R.} and David Pisapia and Weber, {Wolfgang A.} and Souweidane, {Mark M.} and Thomas Reiner",

note = "Publisher Copyright: {\textcopyright} 2017 American Association for Cancer Research.",

year = "2017",

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doi = "10.1158/0008-5472.CAN-16-2850",

language = "English",

volume = "77",

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T1 - Biomarker-based PET imaging of diffuse intrinsic pontine glioma in mouse models

AU - Kossatz, Susanne

AU - Carney, Brandon

AU - Schweitzer, Melanie

AU - Carlucci, Giuseppe

AU - Miloushev, Vesselin Z.

AU - Maachani, Uday B.

AU - Rajappa, Prajwal

AU - Keshari, Kayvan R.

AU - Pisapia, David

AU - Weber, Wolfgang A.

AU - Souweidane, Mark M.

AU - Reiner, Thomas

PY - 2017/4/15

Y1 - 2017/4/15

N2 - 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.

AB - 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.

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U2 - 10.1158/0008-5472.CAN-16-2850

DO - 10.1158/0008-5472.CAN-16-2850

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AN - SCOPUS:85018833104

SN - 0008-5472

VL - 77

SP - 2112

EP - 2123

JO - Cancer Research

JF - Cancer Research

IS - 8

ER -

Biomarker-based PET imaging of diffuse intrinsic pontine glioma in mouse models

Abstract

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