Rationale for and measurement of liposomal drug delivery with hyperthermia using non-invasive imaging techniques

Abstract

The purpose of this review is to present an overview of the state-of-the-art imaging modalities used to track drug delivery from liposomal formulations into tumors during or after hyperthermia treatment. Liposomes are a drug delivery system comprised of a phospholipid bilayer surrounding an aqueous core and have been shown to accumulate following hyperthermia therapy. Use of contrast-containing liposomes in conjunction with hyperthermia therapy holds great promise to be able to directly measure drug dose concentrations as well as to non-invasively describe patterns of drug distribution with MR and PET/SPECT imaging modalities. We will review the rationale for using this approach and the potential advantages of having such information available during and after treatment.

Mathematical spatio-temporal model of drug delivery from low temperature sensitive liposomes during radiofrequency tumour ablation

“…These results compare quantitatively well with our model, though we note that uptake in normal liver cells may be considerably different than in cancer cells. New liposomal formulations that include a contrast agent may provide an effective way for more detailed validation, allowing comparison of spatio-temporal release rates during heating [58]. …”

Biodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer

“…The benefits of DTX/heat additive regimen can be leveraged further by encapsulation into low temperature sensitive liposomes (LTSLs) as a means to enhance tumor delivery compared to free drug alone. LTSLs contain a lysolecithin lipid that rapidly melts and allow release of encapsulated doxorubicin upon being heated to mild hyperthermic temperatures (40-42°C) (9,10). This approach has been shown to result in significant reduction in tumor volume and enhance drug delivery in mouse and rabbit tumor models using water-soluble drugs (e.g., Doxorubicin) compared to conventional free drug or non-thermally sensitive liposome therapy (11)(12)(13)(14)(15).…”

An Imaging-Driven Model for Liposomal Stability and Circulation

“…Positron emission tomography (PET) is a promising non-invasive imaging method to quantify the pharmacokinetics (PK) of radionuclide-labeled particles and drugs in real-time. Using PET, the time-dependent concentration within the blood pool, liver and tumor interstitium can be estimated and PK parameters can be quantified, enabling comparisons in which each subject can serve as its own control1.…”