Radiation-induced multi-organ injury

Abstract

Purpose: Natural history studies have been informative in dissecting radiation injury, isolating its effects, and compartmentalizing injury based on the extent of exposure and the elapsed time post-irradiation. Although radiation injury models are useful for investigating the mechanism of action in isolated subsyndromes and development of medical countermeasures (MCMs), it is clear that ionizing radiation exposure leads to multi-organ injury (MOI).

Methods: The Radiation and Nuclear Countermeasures Program within the National Institute of Allergy and Infectious Diseases partnered with the Biomedical Advanced Research and Development Authority to convene a virtual two-day meeting titled 'Radiation-Induced Multi-Organ Injury' on June 7-8, 2022. Invited subject matter experts presented their research findings in MOI, including study of mechanisms and possible MCMs to address complex radiation-induced injuries.

Results: This workshop report summarizes key information from each presentation and discussion by the speakers and audience participants.

Conclusions: Understanding the mechanisms that lead to radiation-induced MOI is critical to advancing candidate MCMs that could mitigate the injury and reduce associated morbidity and mortality. The observation that some of these mechanisms associated with MOI include systemic injuries, such as inflammation and vascular damage, suggests that MCMs that address systemic pathways could be effective against multiple organ systems.

Keywords: Radiation; medical countermeasures; multi-organ injury.

Figure 1.

Kaplan-Meier survival plots demonstrating dose- and time-dependent lethal sequelae observed after PBI/BM8 in female rats. Rats were irradiated with 13.0–14.5 Gy and moribundity tracked over time. Body weights of rats that received 13.0–14.0 Gy are also shown. The different phases of radiation injury are indicated at top: GI-ARS: GI syndrome of the acute radiation syndrome (ARS); H-ARS: hematopoietic syndrome of ARS; L-DEARE: lung injury delayed effects of acute radiation injury (DEARE); K-DEARE kidney injury DEARE. Reprinted from ‘Rat Models of Partial-body Irradiation with Bone Marrow-sparing (Leg-out PBI) Designed for FDA Approval of Countermeasures for Mitigation of Acute and Delayed Injuries by Radiation,’ by Fish B. L., et al., 2021, Health Physics, 121, pp. 419–433 (Fish et al. 2021). Copyright © 2021 by Health Physics Society. Used with permission.

Figure 2.

Multi-organ comorbidities experienced by animals in the wake Forest university nonhuman primate radiation survivor late effects cohort. Individual morbidities are noted on the outside of the circle and comorbidities are indicated by curves drawn between the segments.