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

Magn Reson Imaging. 2001 Jun;19(5):731-8. doi: 10.1016/s0730-725x(01)00380-0.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Contrast Media*
  • Feasibility Studies
  • Gadolinium DTPA*
  • Humans
  • Hydrogen-Ion Concentration
  • Liposomes
  • Magnetic Resonance Imaging / methods*
  • Sensitivity and Specificity

Substances

  • Contrast Media
  • Liposomes
  • gadodiamide
  • Gadolinium DTPA