title: PARPi-FL--a fluorescent PARP1 inhibitor for glioblastoma imaging.
abstract: New intravital optical imaging technologies have revolutionized our understanding of mammalian biology and continue to evolve rapidly. However, there are only a limited number of imaging probes available to date. In this study, we investigated in mouse models of glioblastoma whether a fluorescent small molecule inhibitor of the DNA repair enzyme PARP1, PARPi-FL, can be used as an imaging agent to detect glioblastomas in vivo. We demonstrated that PARPi-FL has appropriate biophysical properties, low toxicity at concentrations used for imaging, high stability in vivo, and accumulates selectively in glioblastomas due to high PARP1 expression. Importantly, subcutaneous and orthotopic glioblastoma xenografts were imaged with high contrast clearly defining tumor tissue from normal surrounding tissue. This research represents a step toward exploring and developing PARPi-FL as an optical intraoperative imaging agent for PARP1 in the clinic.
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Christopher P
authors: CP
authors: Irwin
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Yasiri
authors: Y
authors: Portorreal
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Christian
authors: C
authors: Brand
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Yachao
authors: Y
authors: Zhang
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Pooja
authors: P
authors: Desai
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Beatriz
authors: B
authors: Salinas
authors: Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Molecular Pharmacology and Chemistry Program, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
authors: Wolfgang A
authors: WA
authors: Weber
authors: Radiochemistry and Imaging Sciences Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA; Center for Molecular Imaging and Nanotechnology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA. Electronic address: reinert@mskcc.org.
authors: Thomas
authors: T
authors: Reiner
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D002460:Cell Line; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D005909:Glioblastoma / Q000473:pathology*; D049452:Green Fluorescent Proteins / Q000737:chemistry / Q000494:pharmacology; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D059906:Neuroimaging / Q000379:methods*; D010793:Phthalazines / Q000737:chemistry / Q000494:pharmacology; D010879:Piperazines / Q000737:chemistry / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
chemical_list: D004791:Enzyme Inhibitors; D010793:Phthalazines; D010879:Piperazines; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D049452:Green Fluorescent Proteins; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; C531550:olaparib