Gadolinium-loaded liposomes allow for real-time magnetic resonance imaging of convection-enhanced delivery in the primate brain

• Published in: Experimental neurology 2005-12, Vol.196 (2), p.381-389
• Main Authors: Saito, Ryuta, Krauze, Michal T., Bringas, John R., Noble, Charles, McKnight, Tracy R., Jackson, Pamela, Wendland, Michael F., Mamot, Christoph, Drummond, Daryl C., Kirpotin, Dimitri B., Hong, Keelung, Berger, Mitchel S., Park, John W., Bankiewicz, Krystof S.
• Format: Article
• Language: English
• Subjects: Animals; Brain - metabolism; CNS; Convection; Convection-enhanced delivery; Drug Delivery Systems; Gadolinium - administration & dosage; Image Processing, Computer-Assisted - methods; Liposomes; Liposomes - metabolism; Macaca fascicularis; Magnetic Resonance Imaging; Male; MRI; Primate; Statistics as Topic; Time Factors; Tissue Distribution
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2005.08.016

Drug delivery to brain tumors has long posed a major challenge. Convection-enhanced delivery (CED) has been developed as a drug delivery strategy to overcome this difficulty. Ideally, direct visualization of the tissue distribution of drugs infused by CED would assure successful delivery of therapeutic agents to the brain tumor while minimizing exposure of the normal brain. We previously developed a magnetic resonance imaging (MRI)-based method to visualize the distribution of liposomal agents after CED in rodent brains. In the present study, CED of liposomes was further examined in the non-human primate brain ( n = 6). Liposomes containing Gadoteridol, DiI-DS, and rhodamine were infused in corona radiata, putamen nucleus, and brain stem. Volume of distribution was analyzed for all delivery locations by histology and MR imaging. Real-time MRI monitoring of liposomes containing gadolinium allowed direct visualization of a robust distribution. MRI of liposomal gadolinium was highly accurate at determining tissue distribution, as confirmed by comparison with histological results from concomitant administration of fluorescent liposomes. Linear correlation for liposomal infusions between infusion volume and distribution volume was established in all targeted locations. We conclude that an integrated strategy combining liposome/nanoparticle technology, CED, and MRI may provide new opportunities for the treatment of brain tumors. Our ability to directly monitor and to control local delivery of liposomal drugs will most likely result in greater clinical efficacy when using CED in management of patients.