FUS/RT: thermal and non-thermal radio-sensitization for improved effectiveness of RT

G. Borasi, Medicine, University of Milano Bicocca, Milano, IT;
A. Melzer, M. Bobeica, D.Xu, Institute for Medical Science and Technology, IMSaT ,University Dundee, UK
G. Russo, F. Vicari, G. Forte, IBFM-CNR -LATO, UOS di Cefalù, Palermo, ITALY;

Objective

By adding HIFUto Radiotherapy (RT), a totally new weapon (FUS/RT) against cancer can be realized. This new therapy retake the benefits of the two methods, but is more than a simple addition of the two. In fact the hyperthermia field and cavitational effects (sonoporation), generated by FUS are a potent enhancers of the radiation effects, and allow a relevant dose reduction and a totally different spatial distribution. In fact HIFU ablation can be reserved to a reduced part of the tumor,in principle to just thehypoxic region, which is nearly insensitive to X-Ray radiation and is generally located in the most internal part of the tumor. It’s well known that the survival of hypoxic cell is the main cause of local recurrence and treatment failure. Having destroyed with HIFU this region, we can administer X-Ray radiation only to the highly oxygenate, annular shaped volume, surrounding the central tumor region, where pathological cells infiltrate healthy tissue. The lower dose level and the reduced irradiation volume drastically reduce the side effects (sequelae)of the radiationtreatment In addition, the FUS opens the door to facilitate mediated drug delivery, eventually, in conjunction with radiation. This combination of therapies, that can be administered to the patient in a short time period, may open a new horizon in patient’s tailored, Medical Oncology.

Methods

We will use an MRgFUS ExAblate 2000 and 2100 CBS with GE Signa 1.5 T with “cradle” for animal support, high resolution 8 channel animal MR coil, biological Laboratory with histology and cell culture capabilities. OEC 9900 C Arm for radiological Imaging, that will be used also as the animal irradiation system, and Siemens Acuson wireless Ultrasound for tumor size control.

The animal model will be severe combined immune deficient (SCID) mice for human tumors and rats in which Dunning R3327-AT prostate tumor, tumor size between 500 and 2500 mm^3. Preliminary: testing animal and tumor grow to different sizes, imaging improvements, optimized HIFU/FUS protocols, animal handling, RT levels and related aspect of the experiment.

1st phase: Safety study: About 1000 mm^3 size tumors, TEST of sham, RT (0.5, 1 and 2 Gy)-one session, MRgFUS one session, RT+HIFU. In the last 3 cases irradiation/ablation of the whole tumor.

Results

While the experimental phase is now in progress, we provide a detailed simulation of the whole treatment, starting with a complete modeling of the thermal field and the effect of radiation sensitization, based on current knowledge. The study arms will allow to compare the efficacy of micro-bubble [2-4] induced versus hyperthermia enhanced radio-sensitivity and to see how combining the effects could be more effective.