Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models
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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
The authors thank Dr. Jason S. Lewis and Dr. Edmund J. Keliher for helpful discussions, Dr. Christian Brand and Christopher P. Irwin for help with experiments and Leah Bassity for editing the manuscript. Technical services provided by the MSKCC Small-Animal Imaging Core Facility, supported in part by NIH Cancer Center Support Grant No 2 P30 CA008748-48, are gratefully acknowledged. NIH Shared Instrumentation Grant No 1S10 OD016207-01, which provided funding support for the purchase of the Inveon PET/CT, is gratefully acknowledged. The authors further thank the Molecular Cytology Core at Memorial Sloan Kettering Cancer Center (P30 CA008748). The authors thank the NIH (K25EB016673 for T.R.), the Brain Tumor Center of Memorial Sloan Kettering Cancer Center (for T.R.), the Center for Molecular Imaging and Nanotechnology (for T.R.), the Clinical and Translational Science Center (CTSC) at Weill Cornell Medical College (NIH/NCATS Grant TL1TR000459 for B.C.), the American-Italian Cancer Foundation (AICF) Post-Doctoral Research Fellowship (for G.C.), the German Research Foundation (for S.K.), as well as the National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT 0965983 at Hunter College) for their generous support.
The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.
Compliance with Ethical Standards
Conflict of Interest
The authors report no conflicts of interest.
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