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Poly (ADP ribose) polymerase (PARP) enzymes generate poly (ADP ribose) post-translational modifications on target proteins for an array of functions centering on DNA and cell stress. PARP isoforms 1 and 2 are critically charged with the surveillance of DNA integrity, and are the first line guardians of the genome against DNA breaks. Here we present a novel probe ([18F]-SuPAR) for non-invasive imaging of PARP-1/2 activity using positron emission tomography (PET). [18F]-SuPAR is a radiofluorinated nicotinamide adenine dinucleotide (NAD) analog that can be recognized by PARP-1/2 and incorporated into the long branched polymers of poly(ADP ribose) (PAR). The measurement of PARP-1/2 activity was supported by a reduction of radiotracer uptake in vivo following PARP-1/2 inhibition with talazoparib treatment, a potent PARP inhibitor currently in Phase III clinical trials, as well as ex vivo co-localization of radiotracer analog and poly (ADP ribose). With [18F]-SuPAR, we were able to map the dose- and time-dependent activation of PARP-1/2 following radiation therapy in breast and cervical cancer xenograft mouse models. Tumor response to therapy was determined by [18F]-SuPAR PET within eight hours of administration of a single dose of radiation equivalent to one round of stereotactic ablative radiotherapy.
This article was published in the following journal.
Name: Bioconjugate chemistry
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Polymerase Chain Reaction (PCR)
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