Chen Qun, Huang Zheng, Luck David, Beckers Jill, Brun Pierre-Herve, Wilson Brian C, Scherz Avigdor, Salomon Yoram, Hetzel Fred W
HealthONE Alliance, Denver, CO 80218, USA.
Photochem Photobiol. 2002 Oct;76(4):438-45. doi: 10.1562/0031-8655(2002)076<0438:PSINCP>2.0.CO;2.
Photodynamic therapy (PDT) uses light to activate a photosensitizer to achieve localized tumor control. In this study, PDT mediated by a second-generation photosensitizer, palladium-bacteriopheophorbide WST09 (Tookad) was investigated as an alternative therapy for prostate cancer. Normal canine prostate was used as the animal model. PDT was performed by irradiating the surgically exposed prostate superficially or interstitially at 763 nm to different total fluences (100 or 200 J/cm2; 50, 100 or 200 J/cm) at 5 or 15 min after intravenous administration of the drug (2 mg/kg). Areas on the bladder and colon were also irradiated. The local light fluence rate and temperature were monitored by interstitial probes in the prostate. All animals recovered well, without urethral complications. During the 1 week to 3 month post-treatment period, the prostates were harvested for histopathological examination. The PDT-induced lesions showed uniform hemorrhagic necrosis and atrophy, were well delineated from the adjacent normal tissue and increased linearly in diameter with the logarithm of the delivered light fluence. A maximum PDT-induced lesion size of over 3 cm diameter could be achieved with a single interstitial treatment. There was no damage to the bladder or rectum caused by scattered light from the prostate. The bladder and rectum were also directly irradiated with PDT. At 80 J/cm2, a full-depth necrosis was observed but resulted in no perforation. At 40 J/cm2, PDT produced minimal damage to the bladder or rectum. On the basis of optical dosimetry, we have estimated that 20 J/cm2 is the fluence required to produce prostatic necrosis. Thus, the normal structure adjacent to the prostate can be safely preserved with careful dosimetry. At therapeutic PDT levels, there was no structural or functional urethral damage even when the urethra was within the treated region. Hence, Tookad-PDT appears to be a promising candidate for prostate ablation in patients with recurrent, or possibly even primary, prostate cancer.
光动力疗法（PDT）利用光激活光敏剂以实现局部肿瘤控制。在本研究中，对由第二代光敏剂钯细菌脱镁叶绿酸WST09（Tookad）介导的光动力疗法作为前列腺癌的替代疗法进行了研究。正常犬前列腺用作动物模型。在静脉注射药物（2mg/kg）后5或15分钟，以763nm对手术暴露的前列腺进行表面或间质照射，达到不同的总能量密度（100或200J/cm2；50、100或200J/cm）。膀胱和结肠区域也进行了照射。通过前列腺间质探头监测局部光能量密度率和温度。所有动物恢复良好，无尿道并发症。在治疗后1周~3个月期间，摘取前列腺进行组织病理学检查。光动力疗法诱导的病变表现为均匀的出血性坏死和萎缩，与相邻正常组织界限清晰，直径随所传递光能量的对数呈线性增加。单次间质治疗可实现直径超过3cm的最大光动力疗法诱导病变大小。前列腺散射光未对膀胱或直肠造成损伤。膀胱和直肠也直接接受了光动力疗法照射。在80J/cm2时，观察到全层坏死，但未导致穿孔。在40J/cm2时，光动力疗法对膀胱或直肠造成的损伤最小。基于光学剂量学，我们估计20J/cm2是产生前列腺坏死所需的能量密度。因此，通过仔细的剂量学可以安全地保留前列腺相邻的正常结构。在治疗性光动力疗法水平下，即使尿道位于治疗区域内，也没有结构或功能性尿道损伤。因此，Tookad光动力疗法似乎是复发性甚至可能是原发性前列腺癌患者前列腺消融的有前景的候选方法。
