Modeling volume effects of experimental brachytherapy in the rat rectum: uncovering the limitations of a radiobiologic concept

A Murine Model for the Study of Molecular Pathogenesis of Radiation Proctitis

“…Radiation was performed with the mice under anesthesia induced by an intraperitoneal injection of ketamine (Clorketam 1000; Vetoquinol), 50 mg/kg, plus xylazine (XYL-M2, veterinary 20 mg/ml VMD) 2 mg/kg. The radiation protocol in this study was adapted from the Norwegian Radium Hospital-Oslo University rat model (16). The brachytherapy system consists of a Varisource high dose rate brachytherapy after-loading unit with a stepping, high-dose-rate Ir-192 source and an 8-mm diameter and a 30-mm-long cylindrical polystyrene applicator.…”

“…Most tissues were harvested 6 to 11 weeks after radiotherapy. The first 10 mice treated with three fractions of 14 Gy, based on the previously described Oslo rat model (16), died within 7 days, with gross evidence of bowel necrosis that was not suitable for histological evaluation. Thereafter, the dose was de-escalated gradually in an attempt to reduce early mortality and to enable study of chronic changes in long-term (>6 weeks) surviving mice.…”

“…Most models of both acute and chronic radiation bowel injury use rats as a model system (15)(16)(17)(18). The use of mice in a model system has two major advantages: (1) the availability of multiple knockout strains and (2) the availability of a wide range of reagents for molecular research.…”

“…Brachytherapy which delivers local radiation to the bowel with minimal exposure of adjacent tissues has been used eloquently in rat models to study the pathogenesis of chronic radiation-induced ulcer and stenosis (16,23,24). We describe a novel mouse brachytherapy model which provides distinct advantages for the modern study of molecular pathways.…”