Thermosensitive paramagnetic liposomes for temperature control during MR imaging-guided hyperthermia: In vitro feasibility studies

Rationale and Objectives. Magnetic resonance (MR) imaging-based temperature monitoring has gained interest for use in general hyperthermia treatment o f tumors. Such therapy requires an accurate control of the temperature, whi ch should range from 41 degrees to 45 degreesC, A novel type of thermosensi tive MR agent is proposed: liposome-encapsulated gadolinium chelates whose temperature response is linked to the phase-transition properties of the li posome carrier. In vitro relaxometry and MR imaging were used to evaluate t he thermosensitivity of the contrast properties of liposomal gadolinium die thylenetriaminepentaacetic acid bis(methylamide) (Gd-DTPA-BMA). Materials and Methods. T1 relaxivity (r1) measurements of liposomal Gd-DTPA -BMA were undertaken at 0.47 T and at temperatures of 20 degrees -48 degree sC. MR imaging was performed at 2.0 T with a gel phantom containing inserts of liposomes. Diffusion-weighted and T1-weighted gradient-recalled echo im ages were acquired as the phantom was heated from 22 degrees to about 65 de greesC. Results. At ambient temperature, the r1 of liposomal Gd-DTPA-BMA was exchan ge limited due to slow water exchange between the liposome interior and ext erior. A sharp, marked increase in r1 occurred as the temperature reached a nd exceeded the gel-to-liquid crystalline phase-transition temperature (T-m ) of the liposomes (42 degreesC). The relaxation enhancement was mainly att ributable to the marked increase in transmembrane water permeability, yield ing fast exchange conditions. There was good correlation between the relaxo metric and imaging results; the signal intensity on T1-weighted gradient-re called echo images increased markedly as the temperature approached T-m. Th e temperature sensitivity of the diffusion-weighted technique differed from that of the liposome-based T1-weighted approach, with an apparent water di ffusion coefficient increasing linearly with temperature, Conclusion. Since the transition from low to high signal intensity occurred in the temperature range of 38 degrees -42 degreesC, the investigated para magnetic liposomes have a potential role as "off-on" switches for temperatu re control during hyperthermia treatment.