Non-invasive magnetic resonance imaging follow-up of sono-sensitive liposome tumor delivery and controlled release after high-intensity focused ultrasound.
This work examines the use of lanthanide-based contrast agents and magnetic resonance imaging in monitoring liposomal behavior in vivo. Dysprosium (Dy) and gadolinium (Gd) chelates, Dy-diethylenetriaminepentaacetic acid bismethylamide (Dy-DTPA-BMA) and Gd-DTPA-BMA, were encapsulated in pegylated distearoylphosphatidylethanolamine-based (saturated) liposomes, and then intravenously injected into Copenhagen rats with subcutaneous Dunning AT2 xenografts. Liposome-encapsulated Dy chelate shortens transverse relaxation times (T(2) and T(2)*) of tissue; thus, liposomal accumulation in the tumor can be monitored by observing the decrease in T(2)* relaxation time over time. The tumor was treated at the time of maximum liposomal accumulation (48 h) with confocal, cavitating high-intensity focused ultrasound to induce liposomal payload release. Using liposome-encapsulated Gd chelate at high enough concentrations and saturated liposomal phospholipids induces an exchange-limited longitudinal (T(1)) relaxation when the liposomes are intact; when the liposomes are released, exchange limitation is relieved, thus allowing in vivo observation of payload release as a decrease in tumor T(1).
LabTAU, Inserm, U1032, Lyon, France; Université de Lyon, Lyon, France; CarMeN, Inserm, U1060, Lyon, France. Electronic address: andrew.fowler@inserm.fr.
Robert Andrew
RA
Fowler
Sigrid L
SL
Fossheim
Jean-Louis
JL
Mestas
Jacqueline
J
Ngo
Emmanuelle
E
Canet-Soulas
Cyril
C
Lafon
D000818:Animals; D045744:Cell Line, Tumor; D003287:Contrast Media; D003692:Delayed-Action Preparations / Q000528:radiation effects; D005500:Follow-Up Studies; D019786:Gadolinium DTPA; D057086:High-Intensity Focused Ultrasound Ablation / Q000379:methods*; D008081:Liposomes / Q000528:radiation effects*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009942:Organometallic Compounds; D004369:Pentetic Acid / Q000031:analogs & derivatives*; D011471:Prostatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D003287:Contrast Media; D003692:Delayed-Action Preparations; D008081:Liposomes; D009942:Organometallic Compounds; C061756:sprodiamide; D004369:Pentetic Acid; C064925:gadodiamide; D019786:Gadolinium DTPA
Cavitation; High-intensity focused ultrasound; Liposomes; Magnetic resonance imaging