A sodium alginate intervention strategy to enhance therapeutic effects of bone-targeted alpha therapy via remodeling 223RaCl2 distribution

Abstract

Radium-223 dichloride is the first approved alpha particle-emitting radiopharmaceutical for patients with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. A large percentage of intestinal enrichment and a slow clearance rate were the main causes of gastrointestinal adverse events after ²²³RaCl₂ administration. The molecular weight of sodium alginate in aqueous solution was determined to be 656 kDa. Sodium alginate exhibits a higher affinity for adsorbing Ra²⁺ compared to other metal ions belonging to the second main group. Sodium alginate as low as 0.5 g/rat reduced intestinal damage by remodeling ²²³RaCl₂ distribution without affecting bone resorption. Intestinal villi were preserved and enterocyte activity was maintained after sodium alginate intervention. Sodium alginate reduced DNA oxidative damage and lipid peroxidation and maintained endogenous antioxidant status by increasing superoxide dismutase levels and total antioxidant capacity. Furthermore, sodium alginate treatment mitigated DNA damage and apoptosis. The administration of sodium alginate effectively maintained the integrity of the intestinal microbiota, which had undergone perturbations due to radiation exposure. This study demonstrated that sodium alginate could be applied to reduce the adverse effects caused by radiation exposure to the intestine during ²²³RaCl₂-treated and reduced intestinal damage resulted from ²²³RaCl₂ accumulation without affecting bone uptake.

Keywords: (223)RaCl(2); Intestinal detox; Intestinal flora; Radiation exposure-induced intestinal injuries; Sodium alginate.