title: Optimal region of the putamen for image-guided convection-enhanced delivery of therapeutics in human and non-human primates.
abstract: Optimal results in the direct brain delivery of brain therapeutics such as growth factors or viral vector into primate brain depend on reproducible distribution throughout the target region. In the present study, we retrospectively analyzed MRI of 25 convection-enhanced delivery (CED) infusions with MRI contrast into the putamen of non-human primates (NHP). Infused volume (V(i)) was compared to total volume of distribution (V(d)) versus V(d) within the target putamen. Excellent distribution of contrast agent within the putamen was obtained in eight cases that were used to define an optimal target volume or "green" zone. Partial or poor distribution with leakage into adjacent anatomical structures was noted in 17 cases, defining "blue" and "red" zones, respectively. Quantitative containment (99±1%) of infused gadoteridol within the putamen was obtained when the cannula was placed in the green zone, 87±3% in the blue zone and 49±0.05% in the red zone. These results were used to determine a set of 3D stereotactic coordinates that define an optimal site for putaminal infusions in NHP and human putamen. We conclude that cannula placement and definition of optimal (green zone) stereotactic coordinates have important implications in ensuring effective delivery of therapeutics into the putamen utilizing routine stereotactic MRI localization procedures and should be considered when local therapies such as gene transfer or protein administration are being translated into clinical therapy.
authors.affiliation: Department of Neurosurgery, University of California San Francisco, 1855 Folsom Street, MCB 226, San Francisco, CA 94103, USA.
authors.forename: Dali
authors.initials: D
authors.lastname: Yin
authors.forename: Francisco E
authors.initials: FE
authors.lastname: Valles
authors.forename: Massimo S
authors.initials: MS
authors.lastname: Fiandaca
authors.forename: John
authors.initials: J
authors.lastname: Bringas
authors.forename: Francisco
authors.initials: F
authors.lastname: Gimenez
authors.forename: Mitchel S
authors.initials: MS
authors.lastname: Berger
authors.forename: John
authors.initials: J
authors.lastname: Forsayeth
authors.forename: Krystof S
authors.initials: KS
authors.lastname: Bankiewicz
mesh_terms: D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D018481:Convection; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008252:Macaca fascicularis; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011699:Putamen / Q000378:metabolism*; D025321:Surgery, Computer-Assisted / Q000379:methods*; D014018:Tissue Distribution
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C062402:gadoteridol; D005682:Gadolinium