Hsi R A, Kapatkin A, Strandberg J, Zhu T, Vulcan T, Solonenko M, Rodriguez C, Chang J, Saunders M, Mason N, Hahn S
Department of Radiation Oncology, Virginia Mason Medical Center, Seattle, Washington 98101, USA.
Clin Cancer Res. 2001 Mar;7(3):651-60.
Our purpose was to determine the feasibility of comprehensive treatment of the canine prostate with photodynamic therapy (PDT) using motexafin lutetium (Lu-Tex) and to evaluate the toxicity and tissue effects associated with this treatment. Twenty-five adult male beagles with normal prostate glands were given an i.v. injection of the second-generation photosensitizer Lu-Tex (2-6 mg/kg). An additional two dogs were used as controls and did not receive any photosensitizing drug. All 27 dogs underwent laparotomy to expose the prostate. Three hours postinjection, a total dose of 75-150 J/cm of 732 nm laser light was delivered interstitially and/or transurethrally to the prostate via cylindrical diffusing fibers. Dogs were euthanized between 2 days and 3 months after PDT. All subjects were monitored for clinical evidence of toxicity. Specimens were examined macroscopically and microscopically to characterize the tissue reaction and assess extent of tissue effect as a result of treatment. Interstitial and/or transurethral PDT were successfully delivered in all dogs with no perioperative complications. No clinical evidence of acute urinary obstruction or rectal bleeding was noted. At all dose levels, macroscopic and microscopic evaluation revealed a prostatic tissue reaction characterized initially (within 48 h) by inflammation and necrosis followed by fibrosis and glandular epithelial atrophy. Comprehensive treatment of the entire prostate could be achieved using the interstitial alone approach or combined transurethral and interstitial approach. The transurethral alone approach did not result in complete coverage of the prostate. Dogs receiving transurethral or combined interstitial and transurethral treatment developed erythema and urethral epithelial disruption at all dose levels. Those receiving combined treatment at the highest dose level (Lu-Tex 6 mg/kg, 150 J/cm light) developed urethral fistulae and peritonitis. Dogs treated with the interstitial alone approach were found to have the least amount of urethral damage. Comprehensive treatment of the canine prostate with Lu-Tex PDT is feasible using an interstitial alone or combined interstitial and transurethral approach. The interstitial alone technique results in the least amount of toxicity. The prostatic tissue reaction to treatment is characterized by initial inflammation and necrosis followed by fibrosis and glandular epithelial atrophy.
我们的目的是确定使用莫特沙芬镥（Lu-Tex）进行光动力疗法（PDT）综合治疗犬前列腺的可行性，并评估该治疗相关的毒性和组织效应。25只前列腺正常的成年雄性比格犬静脉注射第二代光敏剂Lu-Tex（2 - 6mg/kg）。另外两只犬用作对照，未接受任何光敏药物。所有27只犬均接受剖腹手术以暴露前列腺。注射后3小时，通过圆柱形扩散光纤经间质和/或经尿道向前列腺输送75 - 150J/cm²的732nm激光总剂量。在PDT后2天至3个月之间对犬实施安乐死。监测所有受试者的毒性临床证据。对标本进行宏观和微观检查，以表征组织反应并评估治疗导致的组织效应程度。所有犬均成功实施了间质和/或经尿道PDT，无围手术期并发症。未发现急性尿路梗阻或直肠出血的临床证据。在所有剂量水平下，宏观和微观评估均显示前列腺组织反应最初（48小时内）表现为炎症和坏死，随后为纤维化和腺上皮萎缩。单独使用间质方法或联合经尿道和间质方法均可实现对整个前列腺的综合治疗。单独经尿道方法未导致前列腺完全覆盖。接受经尿道或联合间质和经尿道治疗的犬在所有剂量水平下均出现红斑和尿道上皮破坏。接受最高剂量水平联合治疗（Lu-Tex 6mg/kg，150J/cm²光照）的犬出现尿道瘘和腹膜炎。发现单独采用间质方法治疗的犬尿道损伤最少。使用单独的间质方法或联合间质和经尿道方法，用Lu-Tex PDT综合治疗犬前列腺是可行的。单独的间质技术导致的毒性最小。前列腺组织对治疗的反应特征为最初的炎症和坏死，随后是纤维化和腺上皮萎缩。
