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 

Supplementary material

11307_2015_904_MOESM1_ESM.pdf (29.5 mb)
ESM 1Supporting 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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