pH-sensitive paramagnetic liposomes as MRI contrast agents: in vitro feasibility studies.
A novel type of pH-sensitive paramagnetic contrast agent is introduced; a low molecular weight gadolinium (Gd) chelate (GdDTPA-BMA) encapsulated within pH-sensitive liposomes. The in vitro relaxometric properties of the liposomal Gd chelate were shown to be a function of the pH in the liposomal dispersion and the membrane composition. Only a minor pH-dependency of the T1 relaxivity (r1) was observed for liposomal GdDTPA-BMA composed of the unsaturated lipids dioleoyl phosphatidyl ethanolamine (DOPE) and oleic acid (OA). On the other hand, the r1 of GdDTPA-BMA encapsulated within saturated dipalmitoyl phosphatidyl ethanolamine/palmitic acid (DPPE/PA) liposomes demonstrated a strong pH-dependency. At physiological pH and above, the r1 of this system was significantly lowered compared to that of non-liposomal Gd chelate, which was explained by an exchange limited relaxation process. Lowering the pH below physiological value, however, gave a sharp and 6-7 fold increase in r1, due to liposome destabilisation and subsequent leakage of entrapped GdDTPA-BMA. The pH-sensitivity of the DPPE/PA liposome system was confirmed in an in vitro magnetic resonance imaging (MRI) phantom study.
Løkling
K E
KE
Department of Medicinal Chemistry, School of Pharmacy, University of Oslo, Oslo, Norway. Knut-Egil.Lokling@no.nycomed-amersham.com
Fossheim
S L
SL
Skurtveit
R
R
Bjørnerud
A
A
Klaveness
J
J
D003287:Contrast Media; D005240:Feasibility Studies; D019786:Gadolinium DTPA; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes; D008279:Magnetic Resonance Imaging / Q000379:methods*; D012680:Sensitivity and Specificity
D003287:Contrast Media; D008081:Liposomes; C064925:gadodiamide; D019786:Gadolinium DTPA