Biodistribution of [18F]PARPi in healthy ntv-a;p53fl/fl mice 2 h p.i.. Animals were injected with [18F]PARPi 2 hours prior to the biodistribution study (n=4). To control for uptake specificity, one group (n=4) was injected with 1 mg Olaparib 30min prior to the [18F]PARPi injection. The biodistribution shows specific (=blockable) uptake of [18F]PARPi in several organs (e.g. lymph nodes, spleen, pancreas, bone, indicating the presence of PARP1 expressing cells, whereas the uptake in liver and kidney cannot be blocked and is therefore due to excretion processes. N=4 per group, 1 mg Olaparib 30 min prior for blocking. Bl-blood, Br-brain, SG-salivary gland, LN-lymph node, He-heart, Sp-spleen, Pa-pancreas, Li-liver, Ki-kidney, St-stomach, SI-small intestine, LI-large intestine, Mu-muscle, Bo-bone.
Funding
National Institutes of Health
National Science Foundation's Integrative Graduate Education and Research Traineeship
German Research Foundation
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.
