Characterization of a partial-body irradiation model with oral cavity shielding in nonhuman primates

Abstract

Purpose: Characterization of a novel partial-body irradiation (PBI) shielding strategy in nonhuman primates (NHP; rhesus macaques), aimed at protecting the oral cavity, with respect to various gastrointestinal acute radiation syndrome (GI-ARS) syndrome parameters as well as buccal ulceration development.

Materials and methods: NHPs were irradiated using a Cobalt-60 gamma source, in a single uniform dose, ranging from 9–13 Gy and delivered at 0.60–0.80 Gy min⁻¹. Animals were either partially shielded via oral cavity shielding (PBI_OS) or underwent total-body irradiation (TBI).

Results: Clinical manifestations of GI-ARS, and also radiation-induced hematology and clinical chemistry changes, following PBI_OS were comparable to the PBI NHP GI-ARS model utilizing shielding of the distal pelvic limbs and were significantly milder than TBI at similar radiation doses. Nadir citrulline levels were comparable between PBI_OS and TBI but signs of recovery appeared earlier in PBI_OS-treated animals. The PBI_OS model prevented oral mucositis, whereas the TBI model presented buccal ulcerations at all tested radiation dose levels.

Conclusions: Taken together, these results suggest that the PBI_OS model is a suitable alternative to traditional PBI. For GI-ARS investigations requiring orally administered medical countermeasures, PBI_OS confers added value due to the prevention of oral mucositis over traditional PBI.

Keywords:

• Nonhuman primate
• gastrointestinal acute radiation syndrome
• oral mucositis
• partial-body irradiation
• oral cavity shielding

Disclosure statement

None of the authors have any conflict of interest, other than their employment in either a contract research organizations or pharmaceutical company. No information is presented in this paper that advocates for, or promotes, commercial products from any of their organizations.

Additional information

Funding

This work was supported by the National Institute of Allergy and Infectious Diseases contract [NIAID; contract # HHSN272201300030C] awarded to and led by Soligenix, Inc.