Heat-activated liposomal MR contrast agent: initial in vivo results in rabbit liver and kidney.
OBJECTIVE
To evaluate by using in vivo magnetic resonance (MR) imaging the functionality of a liposomal paramagnetic contrast agent with T1 relaxivity that rapidly and markedly increases at temperatures above the gel-to-liquid crystalline phase transition temperature (T(c)) of the liposome membrane.


METHODS
Liposomal gadolinium diethylenetriaminepentaacetic acid bis(methylamide) was injected intravenously at a dose of 0.4 or 1.2 mL (containing 10 or 30 micromol of gadolinium, respectively) per kilogram of body weight shortly before the application of focused ultrasound in liver (seven rabbits) or kidney (three rabbits). VX2 tumors had been implanted in liver in four of the rabbits. Eighteen locations in liver (13 in normal tissue, five in tumor) and 12 locations in kidney were sonicated. MR thermometry was performed during sonications. Signal intensity enhancement was evaluated on T1-weighted images acquired after the tissue cooled, and enhanced zones were compared with isotherms at T(c) of the liposome membrane (approximately 57 degrees C) by using Bland-Altman analysis. In liver, enhanced zones also were compared with areas of histologically verified thermal damage. The threshold temperature of enhancement at T1-weighted imaging was verified by monitoring the signal intensity increase after 10 sonications at varied powers in two locations in normal liver tissue.


RESULTS
Persistent enhancement was observed on T1-weighted images at all sonicated liver locations. In liver, enhanced zones on T1-weighted images were contiguous both with 57 degrees C isotherms (25 measurements; mean difference +/- SD, 0.4 mm +/- 1.2) and with histologically verified areas of necrosis (seven measurements; mean difference +/- SD, 0.1 mm +/- 0.9). The threshold temperature of enhancement at T1-weighted imaging in normal liver was 53 degrees -57 degrees C. In kidney, enhanced zones on T1-weighted images did not match the isotherms.


CONCLUSIONS
The liposomal contrast agent was effective at in vivo MR thermometry in liver but not in kidney.
McDannold
Nathan
N
Department of Radiology, Harvard Medical School and Brigham and Women's Hospital, 221 Longwood Ave, LMRC 007C, Boston, MA 02115, USA. njm@bwh.harvard.edu
Fossheim
Sigrid L
SL
Rasmussen
Henrik
H
Martin
Heather
H
Vykhodtseva
Natalia
N
Hynynen
Kullervo
K
D000818:Animals; D003287:Contrast Media / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004355:Drug Stability; D019786:Gadolinium DTPA / Q000493:pharmacokinetics; D006979:Hyperthermia, Induced; D007668:Kidney / Q000473:pathology*; D008081:Liposomes; D008099:Liver / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000473:pathology* / Q000628:therapy; D008279:Magnetic Resonance Imaging / Q000379:methods*; D009368:Neoplasm Transplantation; D011817:Rabbits; D013696:Temperature
D003287:Contrast Media; D008081:Liposomes; C064925:gadodiamide; D019786:Gadolinium DTPA