Paramagnetic liposomes as thermosensitive probes for MRI-guided thermal treatment: In vitro feasibility studies

In this work the potential of thermosensitive paramagnetic liposomes for in vitro temperature monitoring during radiofrequency heating has been assessed. Two thermosensitive liposome formulations with different phase-transition properties were investigated. Temperature-dependent spin-lattice (T 1) relaxivity measurements were performed at 0.24 T. Magnetic resonance imaging was performed at 2 T in liposome-containing phantom models and T 1 relaxation rates (R 1) were quantified as a function of temperature. Independent temperature measurements were performed using both thermocouple and magnetic-resonance-based methods (proton resonance frequency and diffusion-based thermometry). The relaxometric measurements showed that the T 1 relaxivity increased from low values (about 0.3 s -1mM -1 at 35 °C) to about 4 s -1mM -1 when the temperature approached and exceeded the phase-transition temperature (T c) of the liposome preparations. These data correlated well to the imaging data where an increased signal intensity was observed on T 1-weighted images at temperatures above T c. The derived R 1 maps reflected the measured liposomal temperature sensitivity and temperature quantification was possible on the basis of the measured linear temperature versus R 1 correlation in the transition range of the liposomes. The studies have therefore shown that thermosensitive paramagnetic liposomes exhibit the required temperature sensitivity to allow for an accurate mapping of the temperature changes in an in vitro imaging model. © 2008 Springer-Verlag

Paramagnetic liposomes as thermosensitive probes for MRI-guided thermal treatment: In vitro feasibility studies

In this work the potential of thermosensitive paramagnetic liposomes for in vitro temperature monitoring during radiofrequency heating has been assessed. Two thermosensitive liposome formulations with different phase-transition properties were investigated. Temperature-dependent spin-lattice (T 1) relaxivity measurements were performed at 0.24 T. Magnetic resonance imaging was performed at 2 T in liposome-containing phantom models and T 1 relaxation rates (R 1) were quantified as a function of temperature. Independent temperature measurements were performed using both thermocouple and magnetic-resonance-based methods (proton resonance frequency and diffusion-based thermometry). The relaxometric measurements showed that the T 1 relaxivity increased from low values (about 0.3 s -1mM -1 at 35 °C) to about 4 s -1mM -1 when the temperature approached and exceeded the phase-transition temperature (T c) of the liposome preparations. These data correlated well to the imaging data where an increased signal intensity was observed on T 1-weighted images at temperatures above T c. The derived R 1 maps reflected the measured liposomal temperature sensitivity and temperature quantification was possible on the basis of the measured linear temperature versus R 1 correlation in the transition range of the liposomes. The studies have therefore shown that thermosensitive paramagnetic liposomes exhibit the required temperature sensitivity to allow for an accurate mapping of the temperature changes in an in vitro imaging model. © 2008 Springer-Verlag

Paramagnetic liposomes as thermosensitive probes for MRI-guided thermal treatment: In vitro feasibility studies

In this work the potential of thermosensitive paramagnetic liposomes for in vitro temperature monitoring during radiofrequency heating has been assessed. Two thermosensitive liposome formulations with different phase-transition properties were investigated. Temperature-dependent spin-lattice (T 1) relaxivity measurements were performed at 0.24 T. Magnetic resonance imaging was performed at 2 T in liposome-containing phantom models and T 1 relaxation rates (R 1) were quantified as a function of temperature. Independent temperature measurements were performed using both thermocouple and magnetic-resonance-based methods (proton resonance frequency and diffusion-based thermometry). The relaxometric measurements showed that the T 1 relaxivity increased from low values (about 0.3 s -1mM -1 at 35 °C) to about 4 s -1mM -1 when the temperature approached and exceeded the phase-transition temperature (T c) of the liposome preparations. These data correlated well to the imaging data where an increased signal intensity was observed on T 1-weighted images at temperatures above T c. The derived R 1 maps reflected the measured liposomal temperature sensitivity and temperature quantification was possible on the basis of the measured linear temperature versus R 1 correlation in the transition range of the liposomes. The studies have therefore shown that thermosensitive paramagnetic liposomes exhibit the required temperature sensitivity to allow for an accurate mapping of the temperature changes in an in vitro imaging model. © 2008 Springer-Verlag

Paramagnetic liposomes as thermosensitive probes for MRI-guided thermal treatment: In vitro feasibility studies

In this work the potential of thermosensitive paramagnetic liposomes for in vitro temperature monitoring during radiofrequency heating has been assessed. Two thermosensitive liposome formulations with different phase-transition properties were investigated. Temperature-dependent spin-lattice (T 1) relaxivity measurements were performed at 0.24 T. Magnetic resonance imaging was performed at 2 T in liposome-containing phantom models and T 1 relaxation rates (R 1) were quantified as a function of temperature. Independent temperature measurements were performed using both thermocouple and magnetic-resonance-based methods (proton resonance frequency and diffusion-based thermometry). The relaxometric measurements showed that the T 1 relaxivity increased from low values (about 0.3 s -1mM -1 at 35 °C) to about 4 s -1mM -1 when the temperature approached and exceeded the phase-transition temperature (T c) of the liposome preparations. These data correlated well to the imaging data where an increased signal intensity was observed on T 1-weighted images at temperatures above T c. The derived R 1 maps reflected the measured liposomal temperature sensitivity and temperature quantification was possible on the basis of the measured linear temperature versus R 1 correlation in the transition range of the liposomes. The studies have therefore shown that thermosensitive paramagnetic liposomes exhibit the required temperature sensitivity to allow for an accurate mapping of the temperature changes in an in vitro imaging model. © 2008 Springer-Verlag

Radiosynthesis and biodistribution of cyclic RGD peptides conjugated with novel [¹⁸F] fluorinated aldehyde-containing prosthetic groups

Achieving high-yielding, robust, and reproducible chemistry is a prerequisite for the <sup>18</sup>F-labeling of peptides for quantitative receptor imaging using positron emission tomography (PET). In this study, we extend the toolbox of oxime chemistry to include the novel prosthetic groups [<sup>18</sup>F]-(2-{2-[2-(2-fluoroethoxy)ethoxy]ethoxy}ethoxy)acetaldehyde, [<sup>18</sup>F]5, and [<sup>18</sup>F]-4-(3-fluoropropoxy)benzaldehyde, [<sup>18</sup>F]9, in addition to the widely used 4-[<sup>18</sup>F]fluorobenzaldehyde, [<sup>18</sup>F]12. The three <sup>18</sup>F-aldehydes were conjugated to the same aminooxy-bearing RGD peptide and the effect of the prosthetic group on biodistribution and tumor uptake studied in mice. The peptide conjugate [<sup>18</sup>F]7 was found to possess superior in vivo pharmacokinetics with higher tumor to blood, tumor to liver, tumor to muscle, and tumor to lung ratios than either [<sup>18</sup>F]10 or [<sup>18</sup>F]13. The radioactivity from the [<sup>18</sup>F]7 conjugate excreted more extensively through the kidney route with 79%id passing through the urine and bladder at the 2 h time point compared to around 55%id for the more hydrophobic conjugates [<sup>18</sup>F]10 and [<sup>18</sup>F]13. The chemical nature of a prosthetic group can be employed to tailor the overall biodistribution profile of the radiotracer. In this example, the hydrophilic nature of the ethylene glycol containing prosthetic group [<sup>18</sup>F]5 clearly influences the overall excretion pattern for the RGD peptide conjugate