title: Pulmonary toxicity in a rabbit model of stereotactic lung radiation therapy: efficacy of a radioprotector.
abstract: This study aimed to assess the efficacy of the radioprotector amifostine in limiting radiation toxicity in a rabbit model of lung stereotactic body radiation therapy (SBRT) by correlating contrast-enhanced magnetic resonance angiography (ce-MRA), computed tomography (CT), and helium-3 (He-3) magnetic resonance imaging (MRI) with histopathology. Multiple MRI techniques were tested to obtain complementing physiologic information. Thirteen rabbits received SBRT to the right lower lobe of the lung. Specifically, 4 received 3 × 11 Gray (Gy), 6 received 3 × 11 Gy and 50 mg/kg of amifostine pre-SRBT, and 3 received 3 × 7, 3 × 9, or 3 × 13 Gy. Imaging was performed at baseline and 4, 8, 12, and 16 weeks post-SBRT. Ce-MRA perfusion difference between lungs in the irradiated group at 16 weeks post-treatment was statistically significant (P = .04) whereas the difference in the irradiated + amifostine group was not (P = .30). Histologically observed low red blood cell (RBC) count and CT hypodensity suggests changes were primarily related to perfusion; however, structural changes, such as increased alveolar size, were also present. No changes in He-3 MRI lung ventilation were observed in either group. Although radiation-induced injury detected in rabbits as CT hypodensity contrasted with increased density observed in humans/rodents, the changes in ce-MRA and CT were still significantly reduced after the addition of amifostine to SBRT. Use of CT and selected MRI techniques helped to pinpoint primary physiologic changes.
authors.affiliation: 1Departments of Radiology and 2Radiation-Oncology, University of Virginia, Charlottesville, Virginia.
authors.forename: Jaime
authors.initials: J
authors.lastname: Mata
authors.forename: Ke
authors.initials: K
authors.lastname: Sheng
authors.forename: Klaus
authors.initials: K
authors.lastname: Hagspiel
authors.forename: Kai
authors.initials: K
authors.lastname: Ruppert
authors.forename: Peter
authors.initials: P
authors.lastname: Sylvester
authors.forename: John
authors.initials: J
authors.lastname: Mugler
authors.forename: Carolina
authors.initials: C
authors.lastname: Fernandes
authors.forename: Steven
authors.initials: S
authors.lastname: Guan
authors.forename: James
authors.initials: J
authors.lastname: Larner
authors.forename: Paul
authors.initials: P
authors.lastname: Read
mesh_terms: D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D008279:Magnetic Resonance Imaging / Q000379:methods; D023421:Models, Animal; D011817:Rabbits; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D016634:Radiosurgery / Q000009:adverse effects*; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine
keywords: amifostine; lung radiation; radioprotector