Raman spectroscopy delineates radiation-induced injury and partial rescue by amifostine in bone: a murine mandibular model

Abstract

Despite its therapeutic role in head and neck cancer, radiation administration degrades the biomechanical properties of bone and can lead to pathologic fracture and osteoradionecrosis. Our laboratories have previously demonstrated that prophylactic amifostine administration preserves the biomechanical properties of irradiated bone and that Raman spectroscopy accurately evaluates bone composition ex vivo. As such, we hypothesize that Raman spectroscopy can offer insight into the temporal and mechanical effects of both irradiation and amifostine administration on bone to potentially predict and even prevent radiation-induced injury. Male Sprague–Dawley rats (350–400 g) were randomized into control, radiation exposure (XRT), and amifostine pre-treatment/radiation exposure groups (AMF-XRT). Irradiated animals received fractionated 70 Gy radiation to the left hemi-mandible, while AMF-XRT animals received amifostine just prior to radiation. Hemi-mandibles were harvested at 18 weeks after radiation, analyzed via Raman spectroscopy, and compared with specimens previously harvested at 8 weeks after radiation. Mineral (ρ958) and collagen (ρ1665) depolarization ratios were significantly lower in XRT specimens than in AMF-XRT and control specimens at both 8 and 18 weeks. amifostine administration resulted in a full return of mineral and collagen depolarization ratios to normal levels at 18 weeks. Raman spectroscopy demonstrates radiation-induced damage to the chemical composition and ultrastructure of bone while amifostine prophylaxis results in a recovery towards normal, native mineral and collagen composition and orientation. These findings have the potential to impact on clinical evaluations and interventions by preventing or detecting radiation-induced injury in patients requiring radiotherapy as part of a treatment regimen.

Overcoming Nuclear Winter: The Cutting-edge Science of Bone Healing and Regeneration in Irradiated Fields

“… 27 Furthermore, amifostine pre-treatment preserved bone mineralization to the level of the nonirradiated control 18 weeks following radiotherapy, as there was no statistical difference between the mineral density levels and mineral to collagen ratios between groups. 27 , 28 These results, corroborated with micro-CT analysis, demonstrated that amifostine prophylaxis maintained mineralization metrics (BVF, BMD, and TMD) of irradiated bone to that of the nonirradiated controls. 24 …”

Amifostine Suppresses the Side Effects of Radiation on BMSCs by Promoting Cell Proliferation and Reducing ROS Production

“…This study demonstrated that the depolarization ratios of mineral to collagen were significantly lower in the group that received radiotherapy than in the group that received radiotherapy in conjunction with AMI. Studies using Raman spectroscopy have reported that radiation induces damages to the chemical composition and ultrastructure of bone and prophylaxis with AMI causes a recovery towards the normal, native composition and orientation of the minerals and collagen in bones [46, 47]. In a rat model of radiotherapy with mandibular distraction osteogenesis, the mean bone volume fraction significantly decreased in the group that received radiotherapy alone in comparison to the group that received radiotherapy in conjunction with AMI (0.35 vs. 0.76).…”

Biological and Medical Applications of Multivariate Curve Resolution Assisted Raman Spectroscopy

“…[56][57][58][59][60][61] Raman spectroscopy has been successfully employed to both in vivo and in vitro, and one can easily find its application in various fields of medicine including pathology, 62,63 physiology, 64 virology, 65 urology, 66,67 and dentistry. [68][69][70] Either by using cells, dissected tissues or real time monitoring during surgery, researchers have demonstrated the utility of Raman spectroscopy, particularly in cancers related to brain, 71,72 83,84 Additionally, by analyzing biofluids such as blood and urine, non-invasive diagnostic assays are also being actively developed for many diseases such as diabetes (glucose level monitoring), 85,86 cancer, 87,88 asthma, 89 and malaria. 90,91 Most of these studies relied on univariate analysis (one or two marker bands used for biomolecular identification).…”