PURPOSE

1. MR Guided Focused Ultrasound (MRgHIFU) for Caner Therapy: Enhancement of Drug Delivery in Prostate Tumor in Vivo L Chen, Z Mu, P Hachem, A Konski, G Freedman, A Pollack and C-M Ma Fox Chase Cancer Center, Philadelphia, PA, USA PURPOSE The purpose of this work was to commission and to evaluate the role of MR guided high intensity focused ultrasound (MRgHIFU) in cancer therapy. We specifically focused on investigating the feasibility of the enhancement of drug delivery in prostate cancer for gene therapy with AS-MDM2 and for chemotherapy with both doxorubicin and docetaxel using a nude mice model. The significant enhancement of 3H-Docetaxel delivery in the HIFU treated group is demonstrated in Figure 4. METHOD AND MATERIALS Experiments were carried out using an InSightec ExAblate 2000 HIFU system with a 1.5T GE MR scanner. A phased array transducer is housed in a sealed bath and connected to a motion system. The focal region is cigar shaped, ~3mm in diameter and 10mm in length. The sequence of our studies is as follows. First, we performed experiments on an acoustic phantom to determine the optimal ultrasonic parameters including frequency, acoustic power, and exposure duration. Second, we developed techniques for the treatment of prostate tumor-bearing mice. Third, we evaluated the “optimal” ultrasonic parameters for drug delivery in prostate tumors in mice using doxorubicin. Fourth, based on the “optimal” ultrasonic parameters derived from the doxorubicin experiments we studied the MRgHIFU enhancement of AS-MDM2 in implanted prostate tumor in mice. Finally, we used a radioactive tritiated docetaxel (3H-docetaxel) to determine the uptake in prostate tumor by quantitatively measuring the radioactivity using a liquid scintillator. Figure 2a Comparison of the doxorubicin concentration in tumors with and without HIFU treatment. SD is 0.02 with HIFU and 0.025 without MRgHIFU, respectively. Figure 2b Comparison of the doxorubicin distribution with and without MRgHIFU treatment. Figure 3 An example of H&E staining showing the increased extravasations of blood cells treated with MRgHIFU + ASMDM2 injection (left) compared to that with the ASMDM2 injection only (magnification x 240). MR CT Figure 4 comparison of the concentration of 3H Docetaxel between with and without MRgHIFU treated groups. RESULTS Our preliminary results showed that tissue damage was achieved at the predetermined region through MR real-time guidance (fig.1). Figure 1. Example of an ultrasonic lesion in excised pork meat using MRgHIFU CONCLUSIONS MRgHIFU may have a great potential as a safe, noninvasive treatment modality for cancer therapy including tumor ablation, enhancement of drug livery and boost treatment for hypoxic tumors in combination with radiotherapy. Figure 2a shows the increased doxorubicin concentrations with MRgHIFU treated group compared to that without MRgHIFU treated group. The results is consistent with the distribution of doxorubicin with and without MRgHIFU treatment (fig 2b). Increased extravasations of blood cells were also observed in the treated tumor volume with MRgHIFU + ASMDM2 injection (fig.3). Acknowledgements DOD PC073127 Focused Ultrasound Surgery Foundation