Enhancement of drug delivery in prostate tumor in vivo using MR guided focused ultrasound (MRgHIFU)

Abstract

The purpose of this work is to investigate the effects of pulsed focused ultrasound on the enhancement of 3H-Docetaxel delivery in prostate tumors in vivo. Human prostate cancer LNCaP cells (5 x 105) in 24 ml medium were injected into the prostates of male nude mice. When tumor reached the size of 160 ± 10 mm3 on MRI, HIFU treatment was performed using an InSightec ExAblate 2000 system with a 1.5 T GE MR scanner. The animals were randomly divided into 3 groups (n=8 per group): Group 1, HIFU treatment + 3H-Docetaxel; Group 2, HIFU treatment only and Group 3, as control. For group 1, each mouse was treated with pulsed HIFU under general anesthesia using MR guidance. Immediately after, HIFU treated animals received a single dose of i.v injection of Docetaxel at 15 mg/kg mixed with 3H- Docetaxel at 50 uCi/kg in total volume of 150 μl. Animals in group 2 were treated the same as in group one with the exception of HIFU treatment. Animals were sacrificed 30 minutes after i.v injections and tumors were removed and processed. The radioactivity of 3H-docetaxel in the tumor tissue was quantitatively measured by a liquid scintillation counter. Results showed that all animals tolerated the MRgHIFU treatment well. There were no treatment-related adverse events including skin toxicity. Our data show increased 3H-docetaxel concentration in tumor in the MRgHIFU treated group (1079 ± 132 cmp/75 mg) vs. those without MRgHIFU treatment (524 ± 201 cmp/75 mg) with P = 0.037. We have demonstrated the enhancement of 3H-Docetaxel uptake in implanted prostate tumors with MRgHIFU in vivo. Future studies will be carried out on the efficacy of Docetaxel combined with radiotherapy (RT) to inhibit prostate cancer growth in vivo.