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 disp...

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Bibliographic Details
Published in:Magnetic resonance imaging 2001-06, Vol.19 (5), p.731-738
Main Authors: Løkling, Knut-Egil, Fossheim, Sigrid L, Skurtveit, Roald, Bjørnerud, Atle, Klaveness, Jo
Format: Article
Language:English
Subjects:
Biological and medical sciences
Contrast Media
Contrast media. Radiopharmaceuticals
Exchange limited relaxation
Feasibility Studies
Gadolinium DTPA
Humans
Hydrogen-Ion Concentration
Investigative techniques, diagnostic techniques (general aspects)
Liposomes
Magnetic Resonance Imaging - methods
Medical sciences
Miscellaneous. Technology
Paramagnetic liposomes
pH-sensitivity
Pharmacology. Drug treatments
Phase transitions
Radiodiagnosis. Nmr imagery. Nmr spectrometry
Sensitivity and Specificity
Tumour pH
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Summary: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 T 1 relaxivity (r 1) was observed for liposomal GdDTPA-BMA composed of the unsaturated lipids dioleoyl phosphatidyl ethanolamine (DOPE) and oleic acid (OA). On the other hand, the r 1 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 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 fold 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.
ISSN:0730-725X
1873-5894
DOI:10.1016/S0730-725X(01)00380-0