Multimodal ultrasound mediated drug release model in local cancer therapy

Abstract

Increased cancer survival rates over the last decades are probably less due to advances of a single treatment modality than to optimization of adjuvant treatment procedures. The efficiency of drug delivery in solid tumours is crucial for achieving local tumour control as cytotoxic agents do not target cancer cells selectively. To enhance tumour uptake and selectivity of drugs, liposomally encapsulated microbubbles with drugs or temperature sensitive liposomes with therapeutics have been suggested as new drug delivery vehicles, in combination with ultrasound or hyperthermia, respectively. The presented release model goes beyond simple drug delivery or traditional adjuvant therapies. It represents targeting, real time monitoring and imaging, and exerts concurrent application of therapeutic modalities, within a multimodal treatment regime, thus enhancing synergism. An appropriate diagnostic tool is applied to determine the region of interest with respect to reference coordinates. The delineated region of interest can be modelled by topographic modelling techniques. A subsequent adequate digital tumour model can facilitate an optimal treatment procedure. The system integrates a diagnostic unit with a therapeutic ultrasonic transmitting component, together with a central processing unit, encompassing algorithms for data processing and visualization. Actual drug uptake is based on passive accumulation of drug carriers. Selective drug release of e.g. cytostatic drugs is achieved by ultrasound induced cavitation well defined to the tumour region. Monitoring of drug release can be achieved by imaging techniques. Measurement and monitoring of cavitational activities within the volume of release, and established functional relationships between cavitation level and drug release, will be bridged to various control functions by the processing unit. Further concurrent thermal treatment approaches and ionizing radiation modi are proposed within the comprehensive treatment model. The described multimodal treatment concept has been converted into an actual patient treatment system, and further elucidated into a concrete algorithm for the therapy of patients. Image guided drug release, mediated by focused ultrasound, within a multimodal treatment framework, may localize the effects to the tumour volume and, therefore, allowing for more aggressive therapy, thus enhancing the therapeutic ratio. Integrated image guided drug release systems will probably increase treatment efficacy and survival rates in the future.