Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models
The current study presents [18F]PARPi as imaging agent for PARP1 expression.
[18F]PARPi was generated by conjugating a 2H-phthalazin-1-one scaffold to 4-[18F]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.
[18F]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.
[18F]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.
Key wordsPARP1 Glioblastoma PET Orthotopic Imaging
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