Abstract
Purpose: The current study presents [18F]PARPi as imaging agent for PARP1 expression. Procedures: [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. Results: [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. Conclusions: [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.
Original language | English |
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Pages (from-to) | 386-392 |
Number of pages | 7 |
Journal | Molecular Imaging and Biology |
Volume | 18 |
Issue number | 3 |
DOIs | |
State | Published - Jun 2016 |
Externally published | Yes |
Keywords
- Glioblastoma
- Imaging
- Orthotopic
- PARP1
- PET