@article{62f982061676413484b27861d02774b5,
title = "Discriminating radiation injury from recurrent tumor with [18F]PARPi and amino acid PET in mouse models",
abstract = "Background: Radiation injury can be indistinguishable from recurrent tumor on standard imaging. Current protocols for this differential diagnosis require one or more follow-up imaging studies, long dynamic acquisitions, or complex image post-processing; despite much research, the inability to confidently distinguish between these two entities continues to pose a significant dilemma for the treating clinician. Using mouse models of both glioblastoma and radiation necrosis, we tested the potential of poly(ADP-ribose) polymerase (PARP)-targeted PET imaging with [18F]PARPi to better discriminate radiation injury from tumor. Results: In mice with experimental radiation necrosis, lesion uptake on [18F]PARPi-PET was similar to contralateral uptake (1.02 ± 0.26 lesion/contralateral %IA/ccmax ratio), while [18F]FET-PET clearly delineated the contrast-enhancing region on MR (2.12 ± 0.16 lesion/contralateral %IA/ccmax ratio). In mice with focal intracranial U251 xenografts, tumor visualization on PARPi-PET was superior to FET-PET, and lesion-to-contralateral activity ratios (max/max, p = 0.034) were higher on PARPi-PET than on FET-PET. Conclusions: A murine model of radiation necrosis does not demonstrate [18F]PARPi avidity, and [18F]PARPi-PET is better than [18F]FET-PET in distinguishing radiation injury from brain tumor. [18F]PARPi-PET can be used for discrimination between recurrent tumor and radiation injury within a single, static imaging session, which may be of value to resolve a common dilemma in neuro-oncology.",
keywords = "Amino acid PET, Biomarkers, PARP1, PET/CT, Radiation injury, Radiation necrosis",
author = "Donabedian, {Patrick L.} and Susanne Kossatz and Engelbach, {John A.} and Jannetti, {Stephen A.} and Brandon Carney and Young, {Robert J.} and Weber, {Wolfgang A.} and Garbow, {Joel R.} and Thomas Reiner",
note = "Funding Information: This work was supported by National Institutes of Health grants R01 CA204441 (T.R.), R01 CA155365 (J.R.G), P30 CA008748 (MSK), and P30 CA091842 (Alvin J. Siteman Cancer Center). The authors thank the Tow Foundation and Memorial Sloan Kettering Cancer Center{\textquoteright}s Center for Molecular Imaging & Nanotechnology (B.C. and S.K.), the National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT 0965983 at Hunter College, B.C.), and the Imaging and Radiation Sciences Program (T.R.) for the financial support. Funding Information: The authors thank the support of Memorial Sloan Kettering Cancer Center{\textquoteright}s Animal Imaging Core Facility, Radiochemistry & Molecular Imaging Probes Core Facility, Integrated Genomics Core Facility, and Molecular Cytology Core Facility. Dr. Robert Drzymala and Mr. Jeremy Cates (Radiation Oncology, Washington University) provided assistance with irradiating animals. We thank Dr. Andrei I. Holodny of MSKCC{\textquoteright}s Neuroradiology Service for the invaluable reading of the manuscript; Dr. Carl LeKaye, Dr. Mihaela Lupu, and Mr. Dov Winkleman for their technical support with MR imaging; Dr. Pat Zanzonico and Ms. Valerie Longo for the technical support with PET/CT imaging; Mr. Sherron Hicks for operating the cyclotron; Ms. Arianna Strome and Ms. Meghan Bell for the assistance with immunochemical assays; Dr Lukas Carter and Dr. Laure Michaud for assistance and advice; and Dr. Christian Brand for the chemical precursors. This work was supported by National Institutes of Health grants R01 CA204441 (T.R.), R01 CA155365 (J.R.G), P30 CA008748 (MSK), and P30 CA091842 (Alvin J. Siteman Cancer Center). The authors thank the Tow Foundation and Memorial Sloan Kettering Cancer Center{\textquoteright}s Center for Molecular Imaging & Nanotechnology (B.C. and S.K.), the National Science Foundation Integrative Graduate Education and Research Traineeship (IGERT 0965983 at Hunter College, B.C.), and the Imaging and Radiation Sciences Program (T.R.) for the financial support. The complete data supporting the conclusions of this article are available upon request from the authors. Publisher Copyright: {\textcopyright} 2018, The Author(s).",
year = "2018",
doi = "10.1186/s13550-018-0399-z",
language = "English",
volume = "8",
journal = "EJNMMI Research",
issn = "2191-219X",
}