1. Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models
- Author
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Wolfgang A. Weber, Valentina Di Gialleonardo, Brandon Carney, Valerie A. Longo, Thomas Reiner, Kayvan R. Keshari, Gabriela Chiosis, Giuseppe Carlucci, Beatriz Salinas, Alexander Bolaender, Axel Vansteene, and Susanne Kossatz
- Subjects
0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Biodistribution ,Fluorine Radioisotopes ,Brain tumor ,Poly(ADP-ribose) Polymerase Inhibitors ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,PARP1 ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Radiology, Nuclear Medicine and imaging ,Tissue Distribution ,medicine.diagnostic_test ,business.industry ,Brain Neoplasms ,Magnetic resonance imaging ,Blood Proteins ,medicine.disease ,Magnetic Resonance Imaging ,Imaging agent ,Disease Models, Animal ,030104 developmental biology ,Oncology ,Positron emission tomography ,030220 oncology & carcinogenesis ,Positron-Emission Tomography ,Cancer research ,Autoradiography ,Poly(ADP-ribose) Polymerases ,business ,Glioblastoma ,Tomography, X-Ray Computed ,Half-Life - Abstract
The current study presents [(18)F]PARPi as imaging agent for PARP1 expression.[(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.[(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.[(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.
- Published
- 2015