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      [(18)F]FluorThanatrace uptake as a marker of PARP1 expression and activity in breast cancer.

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          Abstract

          The nuclear enzyme PARP1 plays a central role in sensing DNA damage and facilitating repair. Tumors with BRCA1/2 mutations are highly dependent on PARP1 as an alternative mechanism for DNA repair, and PARP inhibitors generate synthetic lethality in tumors with BRCA mutations, resulting in cell cycle arrest and apoptosis. Zhou et al. recently synthesized an (18)F-labeled PARP1 inhibitor ([(18)F]FluorThanatrace) for PET, and demonstrated high specific tracer uptake in a xenograft model of breast cancer [1]. In the current study, we characterize the level of baseline PARP expression and activity across multiple human breast cancer cell lines, including a BRCA1 mutant line. PARP expression and activity, as measured by levels of PAR and PARP1, is correlated with in vitro [(18)F]FluorThanatrace binding as well as tracer uptake on PET in a xenograft model of breast cancer. Radiotracer uptake in genetically-engineered mouse fibroblasts indicates [(18)F]FluorThanatrace is selective for PARP1 versus other PARP enzymes. This motivates further studies of [(18)F]FluorThanatrace as an in vivo measure of PARP1 expression and activity in patients who would benefit from PARP inhibitor therapy.

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          Author and article information

          Journal
          Am J Nucl Med Mol Imaging
          American journal of nuclear medicine and molecular imaging
          2016
          : 6
          : 1
          Affiliations
          [1 ] Department of Radiology, Perelman School of Medicine, University of Pennsylvania 231 S. 34th Street, Philadelphia, PA 19104, USA.
          [2 ] Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania 231 S. 34th Street, Philadelphia, PA 19104, USA.
          Article
          4749508
          27069769
          5a823c5c-25f7-496d-8b04-befc62aff47d
          History

          BRCA mutation,PARP1,breast cancer
          BRCA mutation, PARP1, breast cancer

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