title: Paramagnetic liposomes as MRI contrast agents: influence of liposomal physicochemical properties on the in vitro relaxivity.
abstract: The in vitro contrast efficacy of liposome encapsulated gadolinium-[10-(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane-1, 4,7-triacetic acid] (GdHPDO3A) has been assessed by relaxometry. The internal concentrations were 150 and 250 mM Gd. Two types of liposome compositions were investigated: a phospholipid blend consisting of both hydrogenated phosphatidylcholine (HPC) and phosphatidylserine (HPS) with a gel-to-liquid crystalline phase transition temperature (Tm) of 50 degrees C, and a mixture of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) with a Tm of 41 degrees C. The investigated liposome size range was 70-400 nm. The T1 and T2 relaxivities (r1 and r2) of liposome encapsulated GdHPDO3A were significantly reduced at 37 degrees C and 0.47 T, compared to those of non-liposomal metal chelate, due to an exchange limitation of the dipolar relaxation process. The highest relaxivity values were obtained for the DPPC/DPPG liposomes, and were attributed to a higher liposome water permeability and to a more efficient water exchange across the membrane. A reduction in liposome size increased the r1, confirming the exchange limited dipolar relaxation. The increased r1 with increasing temperature demonstrated the prerequisite of rapid water exchange between the interior and exterior of the liposome for efficient dipolar relaxation enhancement. Susceptibility effects were present in the liposome systems as the r2/r1 ratio increased with increasing liposome size and internal Gd concentration. In summary, the current work has shown the influence of key physicochemical properties, such as liposome size, membrane composition and permeability, on the in vitro relaxivity of liposome encapsulated GdHPDO3A.
authors.affiliation: Dept. of Medicinal Chemistry, School of Pharmacy, University of Oslo, Norway.
authors.forename: S L
authors.initials: SL
authors.lastname: Fossheim
authors.forename: A K
authors.initials: AK
authors.lastname: Fahlvik
authors.forename: J
authors.initials: J
authors.lastname: Klaveness
authors.forename: R N
authors.initials: RN
authors.lastname: Muller
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003287:Contrast Media; D005682:Gadolinium / Q000008:administration & dosage* / Q000737:chemistry; D006571:Heterocyclic Compounds / Q000008:administration & dosage* / Q000737:chemistry; D008081:Liposomes; D008279:Magnetic Resonance Imaging; D009942:Organometallic Compounds / Q000008:administration & dosage* / Q000737:chemistry; D010316:Particle Size; D010715:Phosphatidylglycerols
chemical_list: D003287:Contrast Media; D006571:Heterocyclic Compounds; D008081:Liposomes; D009942:Organometallic Compounds; D010715:Phosphatidylglycerols; C062402:gadoteridol; D015060:1,2-Dipalmitoylphosphatidylcholine; D005682:Gadolinium; C030345:1,2-dipalmitoylphosphatidylglycerol