Unique Model Development For Precise Targeting Using SARRP
Radiation induced normal tissue damage and toxicity is sometimes an inevitable side effect when treating tumors with radiation therapy. Despite the technological advancements in imaging, treatment planning, and dose delivery, radiation exposure to organs and tissues can be unavoidable. Because of this, some patients experience radiation induced fibrosis, tissue necrosis, and in severe cases complete organ dysfunction. For example, women who receive radiation to the pelvic area to treat cervical cancer almost always experience radiation exposure to the bladder resulting in some level of radiation cystitis (Raja et al., Journal of Urology, 2015). Symptoms of radiation cystitis include reduction in bladder capacity and overall bladder compliance. Furthermore, radiation induced gastrointestinal injury is also a side effect in irradiating lesions located in the pelvic and abdominal region (Andreyev et al. Clinical Oncology, 2007). Symptoms associated with radiation induced gastrointestinal injury include but are not limited to bleeding, nausea, vomiting, pain, and digestive dysfunction. An increased understanding of how to overcome these issues in a preclinical model is necessary for translation into the clinical setting.
Because of these clinical issues, specifically in gastrointestinal injury, a group led by Dr. Constantinos Koumenis at the University of Pennsylvania have set out to investigate better ways to overcome these toxic side effects. Recently a study and publication from his group titled “A novel mouse model to study image-guided, radiation-induced intestinal injury and preclinical screening of radioprotectors” (Verginadis et al. AACR, 2016) has done just that. Due to the scarcity of small animal models for targeted irradiation to the small intestines that mimic clinical care, Verginadis et al. devised a unique mouse model to aid in targeting short intestinal segments using SARRP. In addition, they investigated the effect of Curcumin as an agent to protect the exposed area from radiation induced injury. Previous studies by Dr. Koumenis’ group has shown that curcumin can act as a radiosensitizer in tumor tissues, and as a radioprotector in normal tissues.
As individual segments of the intestinal tract are difficult to identify with CT alone, Verginadis et al. adopted a method of implanting a small radiopaque marker to the jejunum in order to efficiently target radiation with the SARRP (Figures A & B). They further validated radiation targeting through histological analysis of λ-H2AX (Figure C). In addition, TUNEL staining was performed in those mice exposed to RT +/- curcumin. A significant decrease in TUNEL staining (marker for DNA damage) was observed in those mice given curcumin compared to those without (Figure D). These results suggest that curcumin protects against radiation induced injury in both acute and long-term effects.
Overall this study shows that experimental methodology can be adapted to fit within the functional capacity of a small animal image guided micro irradiator such as SARRP. As in the clinic, additional imaging and identification techniques can be adopted for increased targeting accuracy. Furthermore, it sheds light on curcumin, something to be considered in clinical use as a potential radioprotector in patients receiving radiation therapy to the pelvic/abdominal area. Here, Verginadis et al. characterized a novel method to investigate a clinical issue which lacked a preclinical model. Although specific to the intestine, the authors conclude that this model and associated methods should be considered to further characterize radiation response modifiers.
It’s always exciting to see our SARRP users pushing the scientific envelope, and developing novel preclinical methods that have the potential to positively impact a patient’s life. On that note, I’d like to congratulate the group at the University of Pennsylvania on this publication, I’m looking forward to what comes next!
This full article can be found here.