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Optical Imaging of PARP1 in Response to Radiation in Oral Squamous Cell Carcinoma
Susanne Kossatz1, Wolfgang A Weber1,2, Thomas Reiner1,2
1Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, 10065, United States of America.
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.
Insights
New fluorescent probes can visualize Poly (ADP-ribose) polymerase 1 (PARP1) in oral cancer, even after radiation therapy. This imaging tool tracks PARP1 expression and response to DNA damage, aiding in cancer treatment monitoring.
Area of Science:
- Oncology
- Molecular Biology
- Biomedical Imaging
Background:
- Targeting DNA repair pathways, like Poly (ADP-ribose) polymerase 1 (PARP1) inhibition, is crucial for controlling malignant growth.
- Fluorescent small probes are being developed to visualize PARP1 in vivo and monitor PARP1-targeted therapeutics.
- The behavior of these probes in clinical settings with prior DNA damage is not well understood.
Purpose of the Study:
- To evaluate the utility of the fluorescent probe PARPi-FL for imaging PARP1 in oral cancer tissues.
- To assess PARPi-FL uptake in tissues with and without prior DNA damage from radiation therapy.
- To investigate the relationship between DNA damage, PARP1 expression, and PARPi-FL uptake.
Main Methods:
- Utilized the fluorescent imaging agent PARPi-FL.
- Tested PARPi-FL in oral cancer tissues with and without prior induced DNA damage (irradiation).
- Quantified PARP1 expression and PARPi-FL uptake in relation to DNA damage status.
Main Results:
- Demonstrated high PARP1 expression in oral cancer.
- Showed selective uptake of PARPi-FL, independent of prior irradiation.
- Observed increased PARPi-FL uptake correlating with DNA damage and higher PARP1 enzyme expression.
Conclusions:
- PARPi-FL is a valuable tool for imaging PARP1 in oral cancer, even in the context of prior DNA damage.
- The probe's uptake reflects cellular response to DNA damage and PARP1 expression levels.
- Findings support using this imaging approach to measure radiation exposure and monitor treatment effects non-invasively in preclinical cancer models.
