Gene Therapy and Molecular Biology Vol 8, page 509 Gene Ther Mol Biol Vol 8, 509-514, 2004
Feasibility to delineate distribution of solution injected intraprostatic using an ex-vivo canine model Research Article
Charles J. Rosser1, Noriyoshi Tanaka1, R. Jason Stafford2, Roger E. Price3, John D. Hazle2, Motoyoshi Tanaka1, Ashish M. Kamat1, Louis L. Pisters1* 1
Department of Urology, Department of Imaging Physics, 3 Department of Veterinary Medicine and Surgery, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 2
__________________________________________________________________________________ *Correspondence: Louis L. Pisters, M.D., Department of Urology, Unit 446, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030; Phone: 713-792-3250; Fax: 713-794-4824; Email: lpisters@mdanderson.org Key words: prostate, gadolinium, magnetic resonance imaging, gene therapy Abbreviations: dilution of gadolinium DTPA, (Gd-DTPA); Institutional Animal Care and Use Committee, (IACUC); magnetic resonance, (MR)
Charles J. Rosser and Noriyoshi Tanaka contributed equally to the manuscript Supported by the Cancer Center Support Grant CA16672 from the National Cancer Institute and a grant from the American Foundation of Urologic Disease. Received: 5 October 2004; Accepted: 3 November 2004; electronically published: December 2004
Summary We sought to identify an injection scheme and amount of solution injected resulting in optimal distribution of an injected solution into the prostate and to determine whether magnetic resonance (MR) imaging is suitable for evaluating intraprostatic distribution of an injected solution. Freshly excised canine prostates mounted in gelatin were injected under ultrasound guidance with a standard volume (3 ml) of 1:10 dilution of gadolinium DTPA (GdDTPA) and a 1:10 dilution of 1% methylene blue in phosphate-buffered saline. Three different schemes were used: three-core, 10-core, and 20-core injection schemas. The prostates were subsequently imaged by MR imaging. After imaging, samples were fixed in formalin, sectioned transversely, and digitally photographed. The distributions of injected solution on photographs and MR images were compared. Findings on MR images correlated well with photographic findings. Regions of injected solution were generally seen as hyperintense on the T1-weighted images. A 20-core injection scheme distributed the injected solution better than a three-core or 10-core scheme. A 20-core injection scheme resulted in optimal distribution within the prostate of injected methylene blue–Gd-DTPA solution. MR imaging may be useful for imaging the distribution of solution injected into the prostate. the use of ineffective genes or the inability to transduce the desired gene into a sufficient number of tumor cells. Since various genes have been shown to inhibit prostate tumor growth in vitro, (Issacs et al, 1991; Moody, et al, 1994; Vieweg et al, 1994; Gotoh et al, 1997; Steiner et al, 2000) we believe the disappointing clinical results are due to the inability to transduce genes into a sufficient number of tumor cells. In several reports on prostate cancer gene therapy, there is no mention of gene transduction, indicating that transduction may have been low or may not have occurred (Eder et al, 1998; Gulley et al, 1998; Herman et al, 1999; Lu et al, 1999; Pisters et al, 1999; Simons et al, 1999; Belldegrun et al, 2001).
I. Introduction Intraprostatic injection of a therapeutic solution is not a new concept. Specifically, gene therapy for localize/locally advanced prostate cancer routinely relies on intraprostatic injection of vector. Since 1995, more than 55 gene therapy trials have been initiated in patients with prostate cancer (Recombinant DNA Advisory Committee, 2003; Steiner and Gingrich, 2001). The few data we have from such trials demonstrate the feasibility and safety of gene therapy for prostate cancer, but show minimal if any therapeutic benefit (Harrington et al, 2001; Steiner and Gingrich, 2001). The disappointing results may be due to
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