Optical Imaging of PARP1 in Response to Radiation in Oral Squamous Cell Carcinoma

PloS One
Susanne KossatzThomas Reiner

Abstract

Targeting and inhibiting DNA repair pathways is a powerful strategy of controlling malignant growth. One such strategy includes the inhibition of PARP1, a central element in the intracellular DNA damage response. To determine and visualize the expression and intercellular distribution of PARP1 in vivo, and to monitor the pharmacokinetics of PARP1 targeted therapeutics, fluorescent small probes were developed. To date, however, it is unclear how these probes behave in a more realistic clinical setting, where DNA damage has been induced through one or more prior lines of therapy. Here, we use one such imaging agent, PARPi-FL, in tissues both with and without prior DNA damage, and investigate its value as a probe for PARP1 imaging. We show that PARP1 expression in oral cancer is high, and that the uptake of PARPi-FL is selective, irrespective of whether cells were exposed to irradiation or not. We also show that PARPi-FL uptake increases in response to DNA damage, and that this increase is reflected in higher enzyme expression. Our findings provide a framework for measuring exposure of cells to external beam radiation, and could help to elucidate the effects of such treatments non-invasively in mouse models of cancer.

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Citations

Feb 12, 2017·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·X ZhaoX-L Liu
Aug 23, 2017·Proceedings of the National Academy of Sciences of the United States of America·Jun TangThomas Reiner
Jan 1, 2018·Molecular Imaging·Arianna StromeThomas Reiner
Jul 9, 2020·Scientific Reports·Paula Demétrio de Souza FrançaThomas Reiner
Feb 19, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Giacomo PirovanoThomas Reiner
May 7, 2021·European Journal of Nuclear Medicine and Molecular Imaging·Paula Demétrio de Souza FrançaThomas Reiner
May 6, 2017·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Brandon CarneyThomas Reiner
Nov 6, 2018·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Thomas C WilsonBart Cornelissen
Nov 15, 2020·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Paula Demétrio de Souza FrançaElizabeth Jewell

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Methods Mentioned

BETA
xenografts
Flow Cytometry
confocal microscopy
fluorescence imaging
xenograft
flow

Software Mentioned

FlowJo
MetaMorph

Related Concepts

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Carcinoma, Squamous Cell

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