Moore Ronald B, Xiao Zhengwen, Owen Richard J, Ashforth Robert, Dickey Dwayne, Helps Cathy, Tulip John
Department of Surgery, University of Alberta, 2D2.16 Walter Mackenzie Health Sciences Centre, 8440-112 Street, Edmonton, Alberta, Canada T6G 2B7.
Cardiovasc Intervent Radiol. 2008 Jan-Feb;31(1):164-76. doi: 10.1007/s00270-007-9213-4. Epub 2007 Oct 26.
Interstitial photodynamic therapy (PDT) selectively destroys tissue targeted with a photosensitizer and then exposed to light of a specific wavelength. We report a novel delivery method--intra-arterial drug delivery for PDT of the prostate--in a canine model.
To evaluate drug distribution, the prostatovesical artery was selectively cannulated and photosensitizers alone or in conjunction with 99m-technetium-labeled macro-aggregated albumin ((99m)Tc-MAA) were injected via a 3 Fr microcatheter in 8 animals. One dog was followed for 3 months to determine tolerance and toxicity. The remaining animals were euthanized and imaged with whole-body single photon emission CT and gamma counting for radioactivity distribution. Photosensitizer distribution was further analyzed by fluorescence confocal microscopy and tissue chemical extraction. To evaluate PDT, the photosensitizer QLT0074 was infused in 3 animals followed by interstitial illumination with 690 nm laser light.
Intra-arterial infusion selectively delivered drugs to the prostate, with both radioactivity and photosensitizer levels significantly higher (up to 18 times) than in the surrounding organs (i.e., rectum). With unilateral injection of (99m)Tc-MAA, only the injected half of the prostate showed activity whereas bilateral administration resulted in drug delivery to the entire prostate. PDT resulted in comprehensive damage to the prostate without severe complications or systemic toxicity.
Injection of radiolabeled MAA into the prostatovesical artery results in distribution within the prostate with negligible amounts reaching the adjacent organs. PDT also demonstrates selective damage to the prostate, which warrants clinical application in targeted prostate therapies.
间质光动力疗法（PDT）可选择性地破坏用光敏剂靶向并随后暴露于特定波长光线下的组织。我们在犬类模型中报告了一种新型给药方法——用于前列腺PDT的动脉内药物递送。
为评估药物分布，在8只动物中经3Fr微导管选择性地插管至前列腺膀胱动脉，并单独或与99m锝标记的大颗粒白蛋白（（99m）Tc-MAA）联合注入光敏剂。对1只犬随访3个月以确定耐受性和毒性。对其余动物实施安乐死，并使用全身单光子发射CT和γ计数进行放射性分布成像。通过荧光共聚焦显微镜和组织化学提取进一步分析光敏剂分布。为评估PDT，在3只动物中注入光敏剂QLT0074，随后用690nm激光进行间质照明。
动脉内输注可将药物选择性地递送至前列腺，放射性和光敏剂水平均显著高于周围器官（即直肠）（高达18倍）。单侧注射（99m）Tc-MAA时，仅注射侧的前列腺显示有活性，而双侧给药则导致药物递送至整个前列腺。PDT导致前列腺全面受损，但无严重并发症或全身毒性。
将放射性标记的MAA注入前列腺膀胱动脉可使药物在前列腺内分布，而到达相邻器官的量可忽略不计。PDT也显示出对前列腺的选择性损伤，这为其在靶向前列腺治疗中的临床应用提供了依据。
