Real-time visualization and characterization of liposomal delivery into the monkey brain by magnetic resonance imaging.
Liposomes loaded with Gadoteridol, in combination with convection-enhanced delivery (CED), offer an excellent option to monitor CNS delivery of therapeutic compounds with MRI. In previous studies, we investigated possible clinical applications of liposomes to the treatment of brain tumors. In this study, up to 700 microl of Gadoteridol/rhodamine-loaded liposomes were distributed in putamen, corona radiata and brainstem of non-human primates. Distribution was monitored by real-time MRI throughout infusion procedures and allowed accurate calculation of volume of distribution within anatomical structures. We found that different regions of the brain gave various volumes of distribution when infused with the same volume of liposome. Based on these findings, distinct distribution pathways within infused structures can be predicted. This work underlines the importance of monitoring drug delivery to CNS and enables accurate delivery of drug-loaded liposomes to specific brain regions with a standard MRI procedure. Findings presented in this manuscript may allow for modeling of parameters used for direct delivery of therapeutics into various regions of the brain.
Krauze
Michal T
MT
Department of Neurological Surgery, Brain Tumor Research Center, University of California San Francisco, 1855 Folsom Street, Room 226, San Francisco, CA 94103, USA.
Mcknight
Tracy R
TR
Yamashita
Yoji
Y
Bringas
John
J
Noble
Charles O
CO
Saito
Ryuta
R
Geletneky
Karsten
K
Forsayeth
John
J
Berger
Mitchel S
MS
Jackson
Pamela
P
Park
John W
JW
Bankiewicz
Krystof S
KS
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D003287:Contrast Media; D016503:Drug Delivery Systems; D005079:Excipients; D005456:Fluorescent Dyes; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000008:administration & dosage; D008081:Liposomes; D008252:Macaca fascicularis; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage; D012235:Rhodamines
D003287:Contrast Media; D005079:Excipients; D005456:Fluorescent Dyes; D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; D012235:Rhodamines; C062402:gadoteridol; D005682:Gadolinium