journal contribution
posted on 2023-03-31, 01:05 authored by 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 PET/CT whole body image of [18F]PARPi 2 h p.i. Whole body PET/CT images of tumor bearing ntv-a;p53fl/fl mice. The brain tumor can clearly be distinguished from background brain signal. In the body, high uptake can be seen especially in the gut. This is due to the hepatobiliary excretion of the molecule, caused by its high lipophilicity which is necessary in order to reach the target in the cell nucleus.
Funding
National Institutes of Health
National Science Foundation's Integrative Graduate Education and Research Traineeship
German Research Foundation
History
ARTICLE 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. Cancer Res; 77(8); 2112–23. ©2017 AACR.
