title: Preclinical evaluation of a novel device for delivering brachytherapy to the margins of resected brain tumor cavities.
abstract: OBJECTIVE
  The objectives of this study were to evaluate the safety and performance of a new brachytherapy applicator in the treatment of resected brain tumors in a canine model.
  
  
  METHODS
  The brachytherapy applicator is an inflatable balloon catheter that is implanted in the resection cavity remaining after a brain tumor has been debulked. After implantation the balloon is inflated with Iotrex, a sterile solution containing organically bound iodine-125. The low-energy photons emitted by the iodine-125 deposit a therapeutic radiation dose across short distances from the surface of the balloon. After delivery of a prescribed radiation dose to the targeted volume, the radioactive fluid is retrieved and the catheter removed. Small resections of the right frontal lobe were performed in large dogs. Magnetic resonance (MR) images were obtained and used to assess tissue response and to measure the conformance between the resection cavity wall and the balloon surface. In four animals a dose ranging from 36 to 59 Gy was delivered. Neurological status and histological characteristics of the brain were assessed in all dogs. Implantation and explantation as well as inflation and deflation of the device were easily accomplished and well tolerated. The device was easily visualized on MR images, which demonstrated the expected postsurgical changes. The resection cavity and the balloon were highly conformal (range 93-100%). Histological changes to the cavity margin were consistent with those associated with surgical trauma. Additionally, radiation-related changes were observed at the margins of the resection cavity in dogs in which the brain was irradiated.
  
  
  CONCLUSIONS
  This balloon catheter and 125I radiotherapy solution system can safely and reliably deliver radiation to the margins of brain cavities created by tumor resection. Results of this study showed that intracranial pressure changes due to balloon inflation and deflation were unremarkable and characteristic of the imaging properties and radiation safety profile of the device prior to its clinical evaluation. Clinically relevant brachytherapy (adequate target volume and total dose) was accomplished in all four animals subjected to treatment.
authors.affiliation: Prima Therapeutics, Incorporated, Alpharetta, Georgia 30004, USA. jstubbs@proximatherapeutics.com
authors.forename: James B
authors.initials: JB
authors.lastname: Stubbs
authors.forename: Roger H
authors.initials: RH
authors.lastname: Frankel
authors.forename: Karl
authors.initials: K
authors.lastname: Schultz
authors.forename: Ian
authors.initials: I
authors.lastname: Crocker
authors.forename: Dirck
authors.initials: D
authors.lastname: Dillehay
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Olson
mesh_terms: D000818:Animals; D001918:Brachytherapy / Q000295:instrumentation* / Q000379:methods*; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D002404:Catheterization / Q000295:instrumentation / Q000379:methods; D002408:Catheters, Indwelling; D020878:Device Removal; D004195:Disease Models, Animal; D004285:Dogs; D005240:Feasibility Studies; D005625:Frontal Lobe / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D008279:Magnetic Resonance Imaging; D011879:Radiotherapy Dosage