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Molecular Imaging and Biology

, Volume 18, Issue 3, pp 386–392 | Cite as

Non-invasive PET Imaging of PARP1 Expression in Glioblastoma Models

  • Brandon Carney
  • Giuseppe Carlucci
  • Beatriz Salinas
  • Valentina Di Gialleonardo
  • Susanne Kossatz
  • Axel Vansteene
  • Valerie A. Longo
  • Alexander Bolaender
  • Gabriela Chiosis
  • Kayvan R. Keshari
  • Wolfgang A. Weber
  • Thomas Reiner
Research Article

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.

Key words

PARP1 Glioblastoma PET Orthotopic Imaging 

Notes

Acknowledgments

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.

Author Contributions

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.

Supplementary material

11307_2015_904_MOESM1_ESM.pdf (29.5 mb)
ESM 1 Supporting Information. Detailed experimental procedures, characterization data, tables, and figures provide additional documentation of the studies described in this manuscript. (PDF 30246 kb)

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Copyright information

© World Molecular Imaging Society 2015

Authors and Affiliations

  • Brandon Carney
    • 1
    • 2
  • Giuseppe Carlucci
    • 1
  • Beatriz Salinas
    • 1
  • Valentina Di Gialleonardo
    • 1
  • Susanne Kossatz
    • 1
  • Axel Vansteene
    • 1
  • Valerie A. Longo
    • 3
  • Alexander Bolaender
    • 4
  • Gabriela Chiosis
    • 4
  • Kayvan R. Keshari
    • 1
    • 5
    • 6
  • Wolfgang A. Weber
    • 1
    • 5
    • 6
  • Thomas Reiner
    • 1
    • 6
  1. 1.Department of RadiologyMemorial Sloan Kettering Cancer CenterNew York CityUSA
  2. 2.Ph.D. Program in ChemistryThe Graduate Center of the City University of New YorkNew York CityUSA
  3. 3.Small-Animal Imaging Core FacilityMemorial Sloan Kettering Cancer CenterNew York CityUSA
  4. 4.Chemical Biology ProgramMemorial Sloan Kettering Cancer CenterNew York CityUSA
  5. 5.Molecular Pharmacology ProgramMemorial Sloan Kettering Cancer CenterNew York CityUSA
  6. 6.Weill Cornell Medical CollegeNew York CityUSA

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