Dataset Information

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/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.

SUBMITTER: Donabedian PL

PROVIDER: S-EPMC6031550 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Publications

Discriminating radiation injury from recurrent tumor with [<sup>18</sup>F]PARPi and amino acid PET in mouse models.

Donabedian Patrick L PL Kossatz Susanne S Engelbach John A JA Jannetti Stephen A SA Carney Brandon B Young Robert J RJ Weber Wolfgang A WA Garbow Joel R JR Reiner Thomas T

EJNMMI research 20180704 1

<h4>Background</h4>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 po ...[more]

PMID: 29974335

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Project description:PurposeThe aim of our study was to investigate the efficacy of 18F-Fluciclovine brain PET imaging in recurrent gliomas, and to compare the utility of these images to that of contrast enhanced magnetic resonance imaging (MRI) and to [11C-methyl]-L-methionine (11C-Methionine) PET imaging. We also sought to gain insight into the factors affecting the uptake of 18F-FACBC in both tumors and normal brain, and specifically to evaluate how the uptake in these tissues varied over an extended period of time post injection.MethodsTwenty-seven patients with recurrent or progressive primary brain tumor (based on clinical and MRI/CT data) were studied using dynamic 18F-Fluciclovine brain imaging for up to 4 h. Of these, 16 patients also had 11C-Methionine brain scans. Visual findings, semi-quantitative analyses and pharmacokinetic modeling of a subset of the 18F-Fluciclovine images was conducted. The information derived from these analyses were compared to data from 11C-Methionine and to contrast-enhanced MRI.Results18F-Fluciclovine was positive for all 27 patients, whereas contrast MRI was indeterminate for three patients. Tumor 18F-Fluciclovine SUVmax ranged from 1.5 to 10.5 (average: 4.5?±?2.3), while 11C-Methionine's tumor SUVmax ranged from 2.2 to 10.2 (average: 5.0?±?2.2). Image contrast was higher with 18F-Fluciclovine compared to 11C-Methionine (p?<?0.0001). This was due to 18F-Fluciclovine's lower background in normal brain tissue (0.5?±?0.2 compared to 1.3?±?0.4 for 11C-Methionine). 18F-Fluciclovine uptake in both normal brain and tumors was well described by a simple one-compartment (three-parameter: Vb,k1,k2) model. Normal brain was found to approach transient equilibrium with a half-time that varied greatly, ranging from 1.5 to 8.3 h (mean 2.7?±?2.3 h), and achieving a consistent final distribution volume averaging 1.4?±?0.2 ml/cc. Tumors equilibrated more rapidly (t1/2ranging from 4 to 148 min, average 57?±?51 min), with an average distribution volume of 3.2?±?1.1 ml/cc. A qualitative comparison showed that the rate of normal brain uptake of 11C-Methionine was much faster than that of 18F-Fluciclovine.ConclusionTumor uptake of 18F-Fluciclovine correlated well with the established brain tumor imaging agent 11C-Methionine but provided significantly higher image contrast. 18F-Fluciclovine may be particularly useful when the contrast MRI is non-diagnostic. Based on the data gathered, we were unable to determine whether Fluciclovine uptake was due solely to recurrent tumor or if inflammation or other processes also contributed.

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Dataset Information

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

Background

Results

Conclusions

Publications

Discriminating radiation injury from recurrent tumor with [<sup>18</sup>F]PARPi and amino acid PET in mouse models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Background

Results

Conclusions

Publications

Discriminating radiation injury from recurrent tumor with [<sup>18</sup>F]PARPi and amino acid PET in mouse models.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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