Development and Characterization of Novel LipoCEST Agents Based on Thermosensitive Liposomes
Purpose: To develop a novel probe for chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) based on thermosensitive liposomes (lipoCEST) for theranostics, in which diagnostics and therapy are integrated into a single platform. Methods: We developed two kinds of lipoCEST agents...
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Published in | Magnetic Resonance in Medical Sciences Vol. 15; no. 3; pp. 324 - 334 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
Japan
Japanese Society for Magnetic Resonance in Medicine
01.01.2016
Japan Science and Technology Agency |
Subjects | |
Online Access | Get full text |
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Summary: | Purpose: To develop a novel probe for chemical exchange saturation transfer magnetic resonance imaging (CEST MRI) based on thermosensitive liposomes (lipoCEST) for theranostics, in which diagnostics and therapy are integrated into a single platform. Methods: We developed two kinds of lipoCEST agents. The first kind encapsulated dysprosium (Dy)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-Na·3NaCl, terbium-DOTA-Na·3NaCl, or thulium-DOTA-Na·3NaCl into the inner cavity of thermosensitive liposomes, while the second kind encapsulated Dy-DOTA-Na and incorporated amphiphilic metal complex [thulium-diethylenetriamine pentaacetic acid-bis (stearylamide) (Tm-DTPA-BSA)] as a membrane constituent. The nuclear magnetic resonance (NMR)- and Z-spectra of these lipoCEST agents were acquired at various temperatures on a 9.4T MRI scanner. To investigate their applicability to the drug release induced by hyperthermia, we also encapsulated a fluorescent dye (calcein) into the inner cavity of liposomes and measured calcein release after warming them. Results: The intra- and extraliposomal water signals could be differentiated in all agents from their NMR- and Z-spectra. The agent incorporating Tm-DTPA-BSA showed the largest chemical shift (approximately 15 ppm) derived from the intraliposomal water protons. The calcein retained in this agent was successfully released at 44°C. The agent incorporating 30 mol% of Tm-DTPA-BSA in its membrane released more calcein at 42–44ºC than that of the agent incorporating 10 mol%. Conclusion: We developed novel thermosensitive lipoCEST agents and characterized them. Our preliminary results suggest that they are useful and can be applied to theranostics. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1347-3182 1880-2206 |
DOI: | 10.2463/mrms.mp.2015-0039 |