JOURNAL ARTICLE

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

Michal T Krauze, Scott R Vandenberg, Yoji Yamashita, Ryuta Saito, John Forsayeth, Charles Noble, John Park, Krystof S Bankiewicz
Experimental Neurology 2008, 210 (2): 638-44
18295759
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.

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