title: Safety of real-time convection-enhanced delivery of liposomes to primate brain: a long-term retrospective.
abstract: Convection-enhanced delivery (CED) is gaining popularity in direct brain infusions. Our group has pioneered the use of liposomes loaded with the MRI contrast reagent as a means to track and quantitate CED in the primate brain through real-time MRI. When co-infused with therapeutic nanoparticles, these tracking liposomes provide us with unprecedented precision in the management of infusions into discrete brain regions. In order to translate real-time CED into clinical application, several important parameters must be defined. In this study, we have analyzed all our cumulative animal data to answer a number of questions as to whether real-time CED in primates depends on concentration of infusate, is reproducible, allows prediction of distribution in a given anatomic structure, and whether it has long term pathological consequences. Our retrospective analysis indicates that real-time CED is highly predictable; repeated procedures yielded identical results, and no long-term brain pathologies were found. We conclude that introduction of our technique to clinical application would enhance accuracy and patient safety when compared to current non-monitored delivery trials.
authors.affiliation: Laboratory for Molecular Therapeutics, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA 94103, USA.
authors.forename: Michal T
authors.initials: MT
authors.lastname: Krauze
authors.forename: Scott R
authors.initials: SR
authors.lastname: Vandenberg
authors.forename: Yoji
authors.initials: Y
authors.lastname: Yamashita
authors.forename: Ryuta
authors.initials: R
authors.lastname: Saito
authors.forename: John
authors.initials: J
authors.lastname: Forsayeth
authors.forename: Charles
authors.initials: C
authors.lastname: Noble
authors.forename: John
authors.initials: J
authors.lastname: Park
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D001931:Brain Mapping; D018481:Convection; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005682:Gadolinium / Q000008:administration & dosage; D008081:Liposomes / Q000378:metabolism*; D008137:Longitudinal Studies; D008252:Macaca fascicularis / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D012189:Retrospective Studies
chemical_list: D008081:Liposomes; D005682:Gadolinium