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

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

doi:10.1186/s13550-018-0399-z

Abstract

BackgroundRadiation 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.ResultsIn 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.ConclusionsA 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.

Highlights

Radiation injury can be indistinguishable from recurrent tumor on standard imaging
Immunohistochemistry Immunohistochemistry indicates that radiation necrosis lesions and healthy brain express minimal PARP1, whereas U251 tumors overexpress PARP1 in the nuclei of tumor cells (Fig. 2)
Based on the theory that poly(ADP-ribose) polymerase (PARP) overexpression is largely neoplasia-specific in adults, we hypothesized that radiation injury would not present with elevated levels of PARP1 expression

Summary

Introduction

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. Since radiation injury lacks the high proliferation and genomic instability that would drive, or be driven by, PARP overexpression, we theorized that radiation injury would not present with elevated PARP expression Based on this physiological rationale, we formulated the hypothesis that PARPi-PET could accurately distinguish radiation injury from recurrent tumor, and would outperform amino acid PET in differentiating these two important clinical entities (Fig. 1). Two current-generation fluorine-18-labeled PET tracers exist for imaging PARP expression: [18F]PARPi [26] and [18F]FluorThanaTrace [27], with structural similarities to olaparib and rucaparib, respectively

Methods

Results

Discussion

Conclusion