title: Fibrin glue system for adjuvant brachytherapy of brain tumors with 188Re and 186Re-labeled microspheres.
abstract: Brain tumors such as glioblastoma reappear in their original location in almost 50% of cases. To prevent this recurrence, we developed a radiopharmaceutical system that consists of a gel applied immediately after surgical resection of a brain tumor to deliver local radiation booster doses. The gel, which strongly adheres to tissue in the treatment area, consists of fibrin glue containing the beta-emitters rhenium-188 and rhenium-186 in microsphere-bound form. Such microspheres can be prepared by short (2 h or less) neutron activation even in low neutron flux reactors, yielding a mixture of the two beta-emitters rhenium-188 (E(max)=2.1 MeV, half life=17 h) and rhenium-186 (E(max)=1.1 MeV, half life=90.6h). The dosimetry of this rhenium-188/rhenium-186 fibrin glue system was determined using gafchromic film measurements. The treatment efficacy of the radioactive fibrin glue was measured in a 9L-glioblastoma rat model. All animals receiving the non-radioactive fibrin glue died within 17+/-3 days, whereas 60% of the treated animals survived 36 days, the final length of the experiment. Control animals that were treated with the same amount of radioactive fibrin glue, but had not received a previous tumor cell injection, showed no toxic effects over one year. The beta-radiation emitting rhenium-188/rhenium-186-based gel thus provides an effective method of delivering high doses of local radiation to tumor tissue, particularly to wet areas where high adhesive strength and long-term radiation (with or without drug) delivery are needed.
authors.affiliation: Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, Canada. uhafeli@interhange.ubc.ca
authors.forename: Urs O
authors.initials: UO
authors.lastname: Häfeli
authors.forename: Gayle J
authors.initials: GJ
authors.lastname: Pauer
authors.forename: Jaya
authors.initials: J
authors.lastname: Unnithan
authors.forename: Richard A
authors.initials: RA
authors.lastname: Prayson
mesh_terms: D000268:Adhesiveness; D000818:Animals; D001918:Brachytherapy / Q000379:methods*; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004337:Drug Carriers; D015718:Fibrin Tissue Adhesive / Q000737:chemistry*; D005782:Gels; D005909:Glioblastoma / Q000473:pathology / Q000532:radiotherapy*; D007554:Isotopes / Q000008:administration & dosage; D008863:Microspheres; D009368:Neoplasm Transplantation; D011829:Radiation Dosage; D011868:Radioisotopes / Q000008:administration & dosage*; D019275:Radiopharmaceuticals / Q000008:administration & dosage; D018714:Radiotherapy, Adjuvant; D051381:Rats; D017207:Rats, Sprague-Dawley; D012211:Rhenium / Q000008:administration & dosage*; D013997:Time Factors
chemical_list: D004337:Drug Carriers; D015718:Fibrin Tissue Adhesive; D005782:Gels; D007554:Isotopes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium