Brandon Carney1,2, Giuseppe Carlucci1, Beatriz Salinas1, Valentina Di Gialleonardo1, Susanne Kossatz1, Axel Vansteene1, Valerie A Longo3, Alexander Bolaender4, Gabriela Chiosis4, Kayvan R Keshari1,5,6, Wolfgang A Weber1,5,6, Thomas Reiner7,8. 1. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA. 2. Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York City, NY, 10018, USA. 3. Small-Animal Imaging Core Facility, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA. 4. Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA. 5. Molecular Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA. 6. Weill Cornell Medical College, New York City, NY, 10065, USA. 7. Department of Radiology, Memorial Sloan Kettering Cancer Center, New York City, NY, 10065, USA. reinert@mskcc.org. 8. Weill Cornell Medical College, New York City, NY, 10065, USA. reinert@mskcc.org.
Abstract
PURPOSE: The current study presents [(18)F]PARPi as imaging agent for PARP1 expression. PROCEDURES: [(18)F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[(18)F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma. RESULTS: [(18)F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC50 = 2.8 ± 1.1 nM; logPCHI = 2.15 ± 0.41; plasma-free fraction = 63.9 ± 12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82 ± 0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04 ± 0.01 %ID/g. CONCLUSIONS: [(18)F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.
PURPOSE: The current study presents [(18)F]PARPi as imaging agent for PARP1 expression. PROCEDURES: [(18)F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[(18)F]fluorobenzoic acid. Biochemical assays, optical in vivo competition, biodistribution analysis, positron emission tomography (PET)/X-ray computed tomography, and PET/magnetic resonance imaging studies were performed in subcutaneous and orthotopic mouse models of glioblastoma. RESULTS: [(18)F]PARPi shows suitable pharmacokinetic properties for brain tumor imaging (IC50 = 2.8 ± 1.1 nM; logPCHI = 2.15 ± 0.41; plasma-free fraction = 63.9 ± 12.6 %) and accumulates selectively in orthotopic brain tumor tissue. Tracer accumulation in subcutaneous brain tumors was 1.82 ± 0.21 %ID/g, whereas in healthy brain, the uptake was only 0.04 ± 0.01 %ID/g. CONCLUSIONS: [(18)F]PARPi is a selective PARP1 imaging agent that can be used to visualize glioblastoma in xenograft and orthotopic mouse models with high precision and good signal/noise ratios. It offers new opportunities to non-invasively image tumor growth and monitor interventions.
Entities:
Keywords:
Glioblastoma; Imaging; Orthotopic; PARP1; PET
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