Determination of the uptake of AS-bcl-2 in orthotopically grown LNCaP tumors; (c) Determination of the timing of the reduction in MDM2 in orthotopically grown LNCaP tumors;(d) Statistical assessment of targeted antisense therapy on gene expression in tumor bearing

The purpose of this work is to investigate the ef-fects of pulsed focused ultrasound on the enhancement ofH-Docetaxel delivery in prostate tumors in vivo. Human prostatecancer LNCaP cells (5 x 10) in 24 ml medium were injectedinto the prostates of male nude mice. When tumor reached thesize of 160 ± 10 mm on MRI, HIFU treatment was performedusing an InSightec ExAblate 2000 system with a 1.5 T GE MRscanner. The animals were randomly divided into 3 groups(n=8 per group): Group 1, HIFU treatment +H-Docetaxel;Group 2, HIFU treatment only and Group 3, as control. Forgroup 1, each mouse was treated with pulsed HIFU undergeneral anesthesia using MR guidance. Immediately after,HIFU treated animals received a single dose of i.v injection ofDocetaxel at 15 mg/kg mixed with H-Docetaxel at 50 uCi/kg intotal volume of 150 μl. Animals in group 2 were treated thesame as in group one with the exception of HIFU treatment.Animals were sacrificed 30 minutes after i.v injections andtumors were removed and processed. The radioactivity of H-docetaxel in the tumor tissue was quantitatively measured by aliquid scintillation counter. Results showed that all animalstolerated the MRgHIFU treatment well. There were no treat-ment-related adverse events including skin toxicity. Our datashow increasedH-docetaxel concentration in tumor in theMRgHIFU treated group (1079 ± 132 cmp/75 mg) vs. thosewithout MRgHIFU treatment (524 ± 201 cmp/75 mg) with P =0.037. We have demonstrated the enhancement of H-Docetaxel uptake in implanted prostate tumors withMRgHIFU in vivo. Future studies will be carried out on theefficacy of Docetaxel combined with radiotherapy (RT) toinhibit prostate cancer growth in vivo. Keywords— MRgHIFU, Prostate Cancer, Mouse Model, InVivo, Drug Delivery