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Dual-Modality Optical/PET Imaging of PARP1 in Glioblastoma

Abstract

Purpose

The current study presents [18F]PARPi-FL as a bimodal fluorescent/positron emission tomography (PET) agent for PARP1 imaging.

Procedures

[18F]PARPi-FL was obtained by 19F/18F isotopic exchange and PET experiments, biodistribution studies, surface fluorescence imaging, and autoradiography carried out in a U87 MG glioblastoma mouse model.

Results

[18F]PARPi-FL showed high tumor uptake in vivo and ex vivo in small xenografts (< 2 mm) with both PET and optical imaging technologies. Uptake of [18F]PARPi-FL in blocked U87 MG tumors was reduced by 84 % (0.12 ± 0.02 %injected dose/gram (%ID/g)), showing high specificity of the binding. PET imaging showed accumulation in the tumor (1 h p.i.), which was confirmed by ex vivo phosphor autoradiography.

Conclusions

The fluorescent component of [18F]PARPi-FL enables cellular resolution optical imaging, while the radiolabeled component of [18F]PARPi-FL allows whole-body deep-tissue imaging of malignant growth.

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Acknowledgments

The authors thank Drs. Ralph Weissleder (Harvard Medical School), NagaVaraKishore Pillarsetty (MSKCC), and Jason S. Lewis (MSKCC) for helpful discussions. They also thank Beatriz Salinas-Rodriguez for technical assistance, Valerie Longo for assisting with animal experiments, and David Gregory for critical reading of the manuscript. Support was provided by the Animal Imaging Core Facility, the Radiochemistry and Molecular Imaging Probe Core, as well as the Molecular Cytology Core at Memorial Sloan Kettering Cancer Center (P30 CA008748). This work was made possible by a financial contribution from American Italian Cancer Foundation (AICF) and the Clinical and Translational Science Center (CTSC) at Weill Cornell Medical College (NIH/NCATS Grant TL1TR000459). Finally, the authors thank the National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT 0965983 at Hunter College), the NIH (K25EB016673 for T.R.), the Brain Tumor Center of Memorial Sloan Kettering Cancer Center (for T.R.), and the Radiology Development Fund (for T.R.) for their generous funding.

Conflict of Interest

The authors report no conflicts of interest.

Authors’ Contributions

The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Author information

Correspondence to Thomas Reiner.

Additional information

Giuseppe Carlucci and Brandon Carney contributed equally to this work.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

ESM 1

Detailed experimental procedures, characterization data, two tables and seven figures provide additional documentation of the studies described in this manuscript. (PDF 1.68 mb)

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Carlucci, G., Carney, B., Brand, C. et al. Dual-Modality Optical/PET Imaging of PARP1 in Glioblastoma. Mol Imaging Biol 17, 848–855 (2015). https://doi.org/10.1007/s11307-015-0858-0

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Key words

  • PARP1
  • Glioblastoma
  • PET
  • Fluorescence
  • Multimodality
  • Imaging
  • U87 MG