Discriminating radiation injury from recurrent tumor with [18F]PARPi and amino acid PET in mouse models

Patrick L Donabedian; Susanne Kossatz; John A Engelbach; Stephen A Jannetti; Brandon Carney; Robert J Young; Wolfgang A Weber; Joel R Garbow; Thomas Reiner

doi:10.1186/s13550-018-0399-z

Discriminating radiation injury from recurrent tumor with [¹⁸F]PARPi and amino acid PET in mouse models

EJNMMI Res. 2018 Jul 4;8(1):59. doi: 10.1186/s13550-018-0399-z.

Authors

Patrick L Donabedian¹, Susanne Kossatz¹, John A Engelbach², Stephen A Jannetti^{1

3

4}, Brandon Carney^{1

3

5}, Robert J Young^{1

6}, Wolfgang A Weber^{1

7

8}, Joel R Garbow^{2

9}, Thomas Reiner^{10

11}

Affiliations

¹ Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA.
² Department of Radiology, Washington University, St. Louis, MO, USA.
³ Department of Chemistry, Hunter College of the City University of New York, New York, NY, USA.
⁴ Ph.D. Program in Biochemistry, Graduate Center of the City University of New York, New York, NY, USA.
⁵ Ph.D. Program in Chemistry, Graduate Center of the City University of New York, New York, NY, USA.
⁶ Department of Radiology, Weill Cornell Medical College, New York, NY, USA.
⁷ Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
⁸ Department of Nuclear Medicine, Technical University Munich, Munich, Germany.
⁹ Alvin J. Siteman Cancer Center, Washington University, St. Louis, MO, USA.
¹⁰ Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10065, USA. reinert@mskcc.org.
¹¹ Department of Radiology, Weill Cornell Medical College, New York, NY, USA. reinert@mskcc.org.

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/cc_max ratio), while [¹⁸F]FET-PET clearly delineated the contrast-enhancing region on MR (2.12 ± 0.16 lesion/contralateral %IA/cc_max 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.

Abstract

Grants and funding