Paramagnetic liposomes as magnetic resonance imaging contrast agents. Assessment of contrast efficacy in various liver models.
OBJECTIVE
Liposomal gadolinium (Gd)-HP-DO3A has been evaluated as a contrast agent for liver magnetic resonance imaging. The influence of various liposomal physicochemical properties on the liver uptake and contrast efficacy was investigated in various ex vivo and in vivo liver models.


METHODS
Liposomes of different size and membrane properties were prepared. The liposome size ranged from 74 to 304 nm. Two types of phospholipid compositions were studied; a mixture of hydrogenated phosphatidylcholine (HPC) and hydrogenated phosphatidylserine (HPS) with a phase transition temperature (Tm) of 51 degrees C and, a blend composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) displaying a Tm of 41 degrees C. Ex vivo tissue relaxometry and in vivo liver imaging were used to study the influence of liposome composition on the liver uptake and contrast efficacy of intravenously injected liposomes. The influence of liposome size and composition on the kinetics of liver uptake and imaging effect was assessed ex vivo in the perfused rat liver.


RESULTS
The HPC/HPS preparations showed generally a higher and faster liver uptake than the DPPC/DPPG preparations due to a higher stability in blood/perfusate (high Tm) and to the HPS component. The liposome size modulated the extent and kinetics of liver uptake; the larger the size, the faster and more extensive was the liver uptake. Both types of liposome preparations were shown to be efficient liver susceptibility agents both ex vivo and in vivo due to their uptake by the Kupffer cells of liver. The lack of full correlation between the extent of liver uptake and degree of contrast enhancement might be attributed to different regimes of susceptibility-based relaxation.


CONCLUSIONS
The present study has demonstrated the influence of key liposomal physicochemical properties on the liver uptake and contrast efficacy of liposome-encapsulated Gd chelates, exemplified by Gd-HP-DO3A.
Fossheim
S L
SL
Department of Medicinal Chemistry, School of Pharmacy, University of Oslo, Norway.
Colet
J M
JM
Månsson
S
S
Fahlvik
A K
AK
Muller
R N
RN
Klaveness
J
J
D000818:Animals; D003287:Contrast Media; D005682:Gadolinium; D006571:Heterocyclic Compounds / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D008099:Liver / Q000033:anatomy & histology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009942:Organometallic Compounds / Q000737:chemistry; D010743:Phospholipids; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013997:Time Factors
D003287:Contrast Media; D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; D010743:Phospholipids; C062402:gadoteridol; D005682:Gadolinium