Pharmacological management of ionizing radiation injuries: current and prospective agents and targeted organ systems

Abstract

Introduction: There is a limited array of currently available medicinals that are useful for either the prevention, mitigation or treatment of bodily injuries arising from ionizing radiation exposure. Area covered: In this brief article, the authors review those pharmacologic agents that either are currently being used to counter the injurious effects of radiation exposure, or those that show promise and are currently under development. Expert opinion: Although significant, but limited progress has been made in the development and fielding of safe and effective pharmacotherapeutics for select types of acute radiation-associated injuries, additional effort is needed to broaden the scope of drug development so that overall health risks associated with both short-and long-term injuries in various organ systems can be reduced and effectively managed. There are several promising radiation countermeasures that may gain regulatory approval from the government in the near future for use in clinical settings and in the aftermath of nuclear/radiological exposure contingencies. ARTICLE HISTORY

BIO 300: a promising radiation countermeasure under advanced development for acute radiation syndrome and the delayed effects of acute radiation exposure

“…Currently, additional formulations of BIO 300 intended for intramuscular (im) and oral (po) administrations are being developed for use as radioprotectors for H-ARS as well as radiomitigators for DEARE (Table 1 details all products and formulations tested). A large number of studies using animal models have been completed in order to establish the efficacy of these formulations [60]. These studies were performed with different doses of BIO 300 administered parenterally or orally prior to irradiation to evaluate the drug's efficacy against H-ARS.…”

Polypharmacy to Mitigate Acute and Delayed Radiation Syndromes

“…Thus, the TC appeared to accelerate recovery of neutrophils after 10-days, suggesting a similarity to the mechanism reported in mice. GM-CSF accelerated neutrophil recovery as a single agent but different injury model in rats (Cox et al, 2020;Singh and Seed, 2020), justifying its use in the TC. Though mGM-CSF has a very fast half-life in rats (terminal half-life was 1.1 h (Cox et al, 2020), the half-life of PEG mGM-CSF is much longer (terminal half-life of 17.2 h (Cox et al, 2020).…”

Ultrasound-Mediated Gemcitabine Delivery Reduces the Normal-Tissue Toxicity of Chemoradiation Therapy in a Muscle-Invasive Bladder Cancer Model

“…Several radioprotectors have been developed to reduce acute intestinal radiation injury, but most are still in the preclinical phase of development and have not been tested in combination with chemoradiation. 37 This study provides an alternative approach by combining ultrasound-mediated drug delivery with chemoradiation therapy. We showed the efficacy in an orthotopic model of muscle-invasive bladder cancer, which is more clinically relevant than the models used in most chemoradiation preclinical studies, namely ectopic xenograft tumor models, coupled with normal-tissue toxicity studies in the relevant organs that display dose-limiting toxicity.…”