pH-sensitive paramagnetic liposomes as MRI contrast agents: in vitro feasibility studies

A novel type of pH-sensitive paramagnetic contrast agent is introduced; a l ow molecular weight gadolinium (Gd) chelate (GdDTPA-BMA) encapsulated withi n pH-sensitive liposomes. The in vitro relaxometric properties of the lipos omal Gd chelate were shown to be a function of the pH in the liposomal disp ersion and the membrane composition. Only a minor pH-dependency of the T-1 relaxivity (r(1)) was observed for liposomal GdDTPA-BMA composed of the uns aturated lipids dioleoyl phosphatidyl ethanolamine (DOPE) and oleic acid (O A). On the other hand, the r(1) of GdDTPA-BMA encapsulated within saturated dipalmitoyl phosphatidyl ethanolamine/palmitic acid (DPPE/PA) liposomes de monstrated a strong pH-dependency. At physiological pH and above, the r(1) 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 fo ld increase in r(1) 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 . (C) 2001 Elsevier Science Inc. All rights reserved.