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A Pilot Study in Rhesus Macaques to Assess the Treatment Efficacy of a Small Molecular Weight Catalytic Metalloporphyrin Antioxidant (AEOL 10150) in Mitigating Radiation-induced Lung Damage

Garofalo, Michael C.; Ward, Amanda A.; Farese, Ann M.; Bennett, Alexander; Taylor-Howell, Cheryl; Cui, Wanchang; Gibbs, Allison; Prado, Karl L.; MacVittie, Thomas J.*

doi: 10.1097/HP.0b013e3182a4d967
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The objective of this pilot study was to explore whether administration of a catalytic antioxidant, AEOL 10150 (C48H56C15MnN12), could reduce radiation-induced lung injury and improve overall survival when administered after 11.5 Gy of whole thorax lung irradiation in a non-human primate model. Thirteen animals were irradiated with a single exposure of 11.5 Gy, prescribed to midplane, and delivered with 6 MV photons at a dose rate of 0.8 Gy min−1. Beginning at 24 h post irradiation, the AEOL 10150 cohort (n = 7) received daily subcutaneous injections of the catalytic antioxidant at a concentration of 5 mg kg−1 for a total of 4 wk. All animals received medical management, including dexamethasone, based on clinical signs during the planned 180-d in-life phase of the study. All decedent study animals were euthanized for failure to maintain saturation of peripheral oxygen > 88% on room air. Exposure of the whole thorax to 11.5 Gy resulted in radiation-induced lung injury in all animals. AEOL 10150, as administered in this pilot study, demonstrated potential efficacy as a mitigator against fatal radiation-induced lung injury. Treatment with the drug resulted in 28.6% survival following exposure to a radiation dose that proved to be 100% fatal in the control cohort (n = 6). Computed tomography scans demonstrated less quantitative radiographic injury (pneumonitis, fibrosis, effusions) in the AEOL 10150-treated cohort at day 60 post-exposure, and AEOL 10150-treated animals required less dexamethasone support during the in-life phase of the study. Analysis of serial plasma samples suggested that AEOL 10150 treatment led to lower relative transforming growth factor-Beta-1 levels when compared with the control animals. The results of this pilot study demonstrate that treatment with AEOL 10150 results in reduced clinical, radiographic, anatomic, and molecular evidence of radiation-induced lung injury and merits further study as a medical countermeasure against radiation-induced pulmonary injury.

*University of Maryland, School of Medicine, Department of Radiation Oncology, Baltimore, MD 21201.

The authors declare no conflicts of interest.

For correspondence contact: Thomas J. MacVittie, Department of Radiation Oncology, University of Maryland School of Medicine, 10 South Pine Street, MSTF, 6-34E, Baltimore, MD 21201, or email at tmacvittie@som.umaryland.edu.

(Manuscript accepted 1 July 2013)

© 2014 by the Health Physics Society