title: Prophylactic administration of Amifostine protects vessel thickness in the setting of irradiated bone.
abstract: Although often beneficial in the treatment of head and neck cancer (HNC), radiation therapy (XRT) leads to the depletion of vascular supply and eventually decreased perfusion of the tissue. Specifically, previous studies have demonstrated the depletion of vessel volume fraction (VVF) and vessel thickness (VT) associated with XRT. Amifostine (AMF) provides protection from the detrimental effects of radiation damage, allowing for reliable post-irradiation fracture healing in the murine mandible. The purpose of this study is to investigate the prophylactic ability of AMF to protect the vascular network in an irradiated field. Sprague-Dawley rats (n = 17) were divided into 3 groups: control (C, n = 5), radiated (XRT, n = 7), and radiated mandibles treated with Amifostine (AMF XRT, n = 5). Both groups receiving radiation underwent a previously established, human equivalent dose of XRT totaling 35 Gy, equally fractionated over 5 days. The AMF XRT group received a weight dependent (0.5 mg AMF/5 g body weight) subcutaneous injection of AMF 45 min prior to XRT. Following a 56-day recovery period, mandibles were perfused, dissected, and imaged with μCT. ANOVA was used for comparisons between groups and p < 0.05 was considered statistically significant. Stereologic analysis demonstrated a significant and quantifiable restoration of VT in AMF treated mandibles as compared to those treated with radiation alone (0.061 ± 0.011 mm versus 0.042 ± 0.004 mm, p = 0.027). Interestingly, further analysis demonstrated no significant difference in VT between control mandibles and those treated with AMF (0.067 ± 0.016 mm versus 0.061 ± 0.011 mm, p = 0.633). AMF treatment also showed an increase in VVF, however those results were not statistically significant from VVF values demonstrated by the XRT group. Our data support the contention that AMF therapy acts prophylactically to protect vessel thickness. Based on these findings, we support the continued investigation of this treatment paradigm in its potential translation for the prevention of vascular depletion after radiotherapy.
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA. Electronic address: erinpage@umich.edu.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Page
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Felice
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Jose J
authors.initials: JJ
authors.lastname: Rodriguez
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Samir S
authors.initials: SS
authors.lastname: Deshpande
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D008297:Male; D008334:Mandible / Q000187:drug effects / Q000528:radiation effects*; D023421:Models, Animal; D010025:Osteoradionecrosis / Q000517:prevention & control*; D011322:Primary Prevention / Q000379:methods; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine
keywords: Amifostine; Mandible; Osteoradionecrosis; Prophylaxis; Radiotherapy; Vasularity