Tolerance of the spinal cord of rats to irradiation with cyclotron-accelerated helium ions

Abstract

Spinal cords of rats were exposed to either single doses of helium ions ranging from 500 to 3500 rads, or to fractionated doses of helium ions ranging from 1300 to 6530 rads using 10 equal fractions given over 22 days. Both plateau and spread-out Bragg peak regions of ionization were used. For single doses there was no difference betweenplateau or spread-out Bragg peak ionization regions for production of paralysis; thetolerance dose for production of paralysis was about 1900 rads. For the fractionation experiment, there was also no difference between plateau or spread-out Bragg peak ionization regions for production of paralysis; the tolerance dose was between 5220 and 6530rads. Comparison of dose levels producing about 10% partial paralysis indicates that about 500 rads of dose is recovered between fractions. In both single dose and fractionated experiments, latency between onset of paralysis was between 20 to 24 weeks.

Fractionated carbon ion irradiations of the rat spinal cord: comparison of the relative biological effectiveness with predictions of the local effect model

“…However, especially late effects do not solely result from inactivation of cell populations [24, 25] and it is therefore important to benchmark RBE-models additionally in vivo. For this, the rat spinal cord is an established model [9–11, 26, 27] providing a well-detectable endpoint and a volume-independent response, if the irradiated segment is larger than 8 mm [28]. Hence, our study measures the RBE for the local radiation quality related to the only marginal LET-variation within the cross-section of the rat spinal cord.…”

Pathology of radiation myelopathy

“…18,28,34,64 Linear energy transfer Linear energy transfer (LET) is the energy that ionizing radiation gives to surrounding tissues per unit length of track. A high-LET beam, such as α particles, fast neutrons, and heavy ions, has been shown to have a larger relative biological effectiveness (RBE: the ratio of the dose necessary to induce a certain biological effect to the dose of X-ray necessary to induce the same biological effect 15,16,25,38 In Germany and Japan, clinical trials of heavy ion radiation therapy of malignant tumors have been going on. The tolerable dose must be determined after a careful consideration of experimental data.…”

“…RBE correlates with LET until LET exceeds 100 keV/μm. High‐LET beams have a large RBE for radiation myelopathy in laboratory animals 13–16,24,25,27,38,64 . RBE of high‐LET beams are approximately 1.2–3.0 for fast neutrons 13,14,24,27 and 1.2–2.2 for heavy ions such as neon and carbon ion 15,16,25,38 …”

“…Most cases of clinically reported radiation myelopathy occurred when the cervical or thoracic spinal cord was included in the radiation field by mistake during the radiotherapy of carcinoma of the lung, 5,6,10,11 esophagus, 9,10 or other head and neck tumors 2,3,10 . It has also been investigated experimentally in laboratory animals, 12–38 because the occurrence of injury in the spinal cord is detected more easily by the onset of paralysis than in cranial irradiation, and much information on the pathogenesis of radiation myelopathy has been accumulated. Dual mechanisms for the pathogenesis of radiation myelopathy have been proposed depending on whether the major targets of irradiation are glial cells, especially oligodendrocytes (glial theory), or vascular endothelium (vascular hypothesis).…”

Relative biological effectiveness of oxygen ion beams in the rat spinal cord: Dependence on linear energy transfer and dose and comparison with model predictions

“…the central nervous system (CNS). A number of studies have been performed in the rat spinal cord positioned in the entrance and SOBP regions [17] , [18] , [19] , [20] , [21] , [22] . While these studies initially focused on helium ions, they were extended to carbon and neon ion beams employing either single, 4 or 8 (only neon) fractions (Fx) [22] .…”