Paramagnetic thermosensitive liposomes for MR-thermometry

Abstract

MR-thermometry methods have been developed for the guidance and control of thermal therapies such as thermal ablation or regional hyperthermia. However, they are limited to the measurement of temperature changes and, thus, cannot be used to assess absolute temperature values. Paramagnetic thermosensitive liposomes are innovative contrast agents offering the potential to overcome these limitations. They are composed of a gadolinium- or manganese-based compound enclosed by a phospholipid membrane with a distinct gel-to-liquid crystalline phase transition temperature (T_m). At this temperature, the phospholipid membrane changes from a gel-phase to a liquid-crystalline phase which is associated with an increased transmembrane permeability towards solutes and water. Under these conditions, both types of paramagnetic thermosensitive liposomes demonstrate a significant increase in longitudinal (T1) relaxivity, attributed to the release of paramagnetic material from the liposome and/or to the increased water exchange rate between the liposome interior and exterior. Paramagnetic thermosensitive liposomes have already been successfully studied in animal models and have demonstrated a clear correlation between tissue temperature changes and signal intensity changes in MRI. Nevertheless, before entering clinical trials they have to be studied in more detail with regard to dose, pharmacokinetics and toxicity.

• Paramagnetic liposomes
• thermometry
• contrast agent
• relaxivity
• magnetic resonance (MR)
• Abbreviations: Chol, Cholesterol
• CT, computed tomography
• D, diffusion coefficient
• DOX, doxorubicin
• DPPC, dipalmitoyl-sn-glycero-3-phosphocholine
• DPPG, 1.2-dipalmitoyl-sn-glycero-3-phosphoglycerol
• DPPGOG, 1.2-dipalmitoyl-sn-glycero-3-phosphoglyceroglycerol
• DSC, differential scanning calorimetry
• DSPC, 1.2-distearoyl-sn-glycero-3-phosphocholine
• DSPE-PEG2000, 1.2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[poly(ethyleneglycol)2000]
• DSPG, 1.2-distearoyl-sn-glycero-3-phosphoglycerol
• Gd, gadolinium
• Gd-DOTA, gadolinium tetraazacyclododecanetetraacetic acid
• Gd-DTPA, gadolinium diethylenetriaminepentaacetic acid
• Gd-DTPA-BMA, Gd diethylenetriaminepentaacetic acid bis(methylamide)
• Gd-HP-DO3A, Gd-[10-(2-hydroxypropyl)-1.4.7.10-tetraazacyclododecane-1.4.7-triacetic acid]
• HPC, hydrogenated phosphatidylcholine
• HPS, hydrogenated phosphatidylserine
• LD 50, 50% lethal dose
• Mn, manganese
• MPS, mononuclear phagocyte system
• MR, magnetic resonance
• MRI, MR imaging
• MRS, MR spectroscopy
• MSPC, 1-stearoyl-2-hydroxy-sn-glycero3-phosphochline
• PEG, poly(ethylene) glycol
• PRF, chemical shift of the proton resonance frequency
• RF, radiofrequency
• SD, standard deviation
• T1, longitudinal relaxation time of water protons
• Tm, gel-to-liquid crystalline phase temperature
• TSL, thermosensitive liposomes