Safety of real-time convection-enhanced delivery of liposomes to primate brain: A long-term retrospective

• Published in: Experimental neurology Vol. 210; no. 2; pp. 638 - 644
• Main Authors: Krauze, Michal T., Vandenberg, Scott R., Yamashita, Yoji, Saito, Ryuta, Forsayeth, John, Noble, Charles, Park, John, Bankiewicz, Krystof S.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.04.2008; Elsevier
• Subjects: Animals; Biological and medical sciences; Brain - metabolism; Brain Mapping; Convection; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Dose-Response Relationship, Drug; Drug Delivery Systems; Gadolinium - administration & dosage; Liposomes - metabolism; Longitudinal Studies; Macaca fascicularis - anatomy & histology; Magnetic Resonance Imaging - methods; Male; Medical sciences; Neurology; Primates; Retrospective Studies; Vertebrata; Nervous system diseases; Mammalia; Central nervous system; Liposome; Primates; Safety; Long term; Convection; Retrospective; Encephalon
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2007.12.015

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.