Biological effects of high-LET irradiation on the circulatory system.

Purpose: High-linear energy transfer (LET) radiation is generally thought to be more biologically effective in various tissues than low-LET radiation, but whether this also applies to the circulatory system remains unclear. We therefore reviewed biological studies about the effects of high-LET radiation on the circulatory system.

Conclusions: We identified 76 relevant papers (24 in vitro, 2 ex vivo, 51 in vivo, one overlapping). In vitro studies used human, bovine, porcine or chick vascular endothelial cells or cardiomyocytes, while ex vivo studies used porcine hearts. In vivo studies used mice, rats, rabbits, dogs or pigs. The types of high-LET radiation used were neutrons, α particles, heavy ions and negative pions. Most studies used a single dose, although some investigated fractionation effects. Twenty-one studies estimated the relative biological effectiveness (RBE) that ranged from 0.1 to 130, depending on radiation quality and endpoint. A meta-analysis of 6 in vitro and 8 in vivo studies (selected based on the feasibility of estimating the RBE and its uncertainty) suggested an RBE of 6.69 (95% confidence intervals (CI): 2.51, 10.88) for in vitro studies and 1.14 (95% CI: 0.91, 1.37) for in vivo studies. The meta-analysis of these 14 studies yielded an RBE of 2.88 (95% CI: 1.52, 4.25). This suggests that high-LET radiation is only slightly more effective than low-LET radiation, although substantial inter-study heterogeneity complicates interpretation. Therapeutic effects have also been reported in disease models. Further research is needed to better understand the effects on the cardiovascular system and to improve radiation protection.