title: MR-guided focused ultrasound: enhancement of intratumoral uptake of [³H]-docetaxel in vivo.
abstract: The purpose of this study is to quantify the enhancement of [³H]-docetaxel in implanted prostate tumors treated with MR-guided pulsed focused ultrasound (MRgFUS). Human prostate cancer, LNCaP cells in 25 µl, were implanted into the prostates of male nude mice. The tumor growth was directly monitored on MRI. When the tumor reached a designated size, MRgFUS treatment was performed using a focused ultrasound treatment system (InSightec ExAblate 2000) with a 1.5 T GE MR scanner. The tumor-bearing animals were randomly divided into three groups: group 1, MRgFUS treatment + [³H]-docetaxel; group 2, [³H]-docetaxel only and group 3, as a control. Animals in group 1 were treated with MRgFUS non-invasively. Immediately after the treatment, the animals received a single dose of tail vein injection of docetaxel at 15 mg kg⁻¹ mixed with [³H]-docetaxel at 50 uCi kg⁻¹ in a total volume of 150 µl. Animals in group 2 were treated the same as in group one, however without MRgFUS treatment. Animals in group 3 were treated as a control. Animals were sacrificed 30 min after i.v. injections regardless of whether or not they received focused ultrasound. Tumors were removed and processed. The radioactivity of [³H]-docetaxel in the tumor tissue was quantitatively measured by a liquid scintillation counter. Our study showed that all animals tolerated the MRgFUS treatment well. Our data showed increased (³H-docetaxel concentration in the tumor in the MRgFUS-treated group (1079 ± 132 cmp/75 mg) versus those without MRgFUS treatment (524 ± 201 cmp/75 mg) with P = 0.037.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA. lili.Chen@fccc.edu
authors.forename: Lili
authors.initials: L
authors.lastname: Chen
authors.forename: Zhaomei
authors.initials: Z
authors.lastname: Mu
authors.forename: Paul
authors.initials: P
authors.lastname: Hachem
authors.forename: C-M
authors.initials: CM
authors.lastname: Ma
authors.forename: Annie
authors.initials: A
authors.lastname: Wallentine
authors.forename: Alan
authors.initials: A
authors.lastname: Pollack
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D001692:Biological Transport; D002199:Capillary Permeability; D045744:Cell Line, Tumor; D000077143:Docetaxel; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000628:therapy*; D043823:Taxoids / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D013696:Temperature; D013821:Thermometers; D013997:Time Factors; D014316:Tritium; D014464:Ultrasonic Therapy / Q000379:methods*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D043823:Taxoids; D014316:Tritium; D000077143:Docetaxel