MRI monitoring of intratumoral drug delivery and prediction of the therapeutic effect with a multifunctional thermosensitive liposome

Tagami, Tatsuaki, Foltz, Warren D., Ernsting, Mark J., Lee, Carol M., Tannock, Ian F., May, Jonathan P. and Li, Shyh Dar (2011) MRI monitoring of intratumoral drug delivery and prediction of the therapeutic effect with a multifunctional thermosensitive liposome. Biomaterials, 32 (27), 6570-6578. (doi:10.1016/j.biomaterials.2011.05.029).

Abstract

Non-invasive in vivo imaging of drug distribution enables real-time monitoring and prediction of therapeutic responses to treatment. We have developed a thermosensitive liposomal formulation (HaT: Hyperthermia-activated-cytoToxic) consisting of DPPC and Brij78, a formulation that enhanced drug delivery compared to the lyso-lipid temperature sensitive liposomes (LTSL). Here we report the development of a multifunctional HaT liposome co-encapsulating Gd-DTPA (an MRI probe) and doxorubicin (DOX), which simultaneously releases and reports on drug delivery in a locally heated tumor. The temperature-dependent release profiles of DOX from HaT were closely related to the change in the MR T₁ relaxation time, in which DOX was 100% released at 40-42 °C in 3 min, accompanied by a 60% reduction in T₁. By T₁ relaxometry analysis, no Gd-DTPA leakage was detected in 30 min at 30-37 °C. In the in vivo study, DOX uptake in the tumor was quantitatively correlated with T₁ response (R² = 0.98) and the patterns of the T₁ image and the intratumoral DOX uptake were matched, in which both signals were predominantly detected in the highly perfused tumor periphery. Finally, the extent of T₁ relaxation enhancement in the heated tumor successfully predicted the antitumor efficacy in a standard pharmacological response model (R² = 0.98).

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Contributors

Author: Jonathan P. May

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