Prostate Pre-Clinical

传统的前列腺癌疗法有时不能提供令人满意的治疗结果， 而副作用通常显著降低患者的生活质量。更局限的癌症 具有最小副作用的治疗模式是前列腺癌管理所需要的。 光动力疗法（PDT）利用局部递送的光能来激活预先施用的光致抗蚀剂。 光敏剂，其最终导致靶组织的受控破坏。我们的目标， 因此，开发PDT作为前列腺癌的替代/替代疗法， 消融术具体目的是：（1）优化前列腺PDT治疗方案 采用大鼠Dunning肿瘤模型以及正常和预辐照犬 前列腺，（2）确定由不同光敏剂产生的PDT损伤阈值， （3）开发治疗计划和监测技术， 用于精确前列腺消融的光学探针，以及（4）在体内验证程序 全前列腺切除术的模型。对于上述调查，我们建议采用一种独特的 第二代光敏剂Tookad，主要作用于局部血管系统，和 在给药和光照射之间实际上不需要等待时间。这种敏化剂 从体内迅速清除，并基本上从所有重要组织中完全清除 在一天之内。我们将定性评价光敏剂的药代动力学。光学 探针将用于测量动态光通量分布和组织氧合， PDT。PDT诱导的病变将进行组织病理学评价，并与治疗相关 用于损伤阈值的剂量测定。将对相邻的患者进行类似的手术。 结构.根据研究所得的阈值和资料，我们会 发展治疗计划和监测技术，以实现我们的最终目标：全前列腺 对邻近结构损伤最小的消融。这些程序随后将在 用电离辐射预处理的犬前列腺，以模拟 常规放射治疗失败了因此，该项目的完成将提供 医生直接适用的信息和技术，以计划PDT的临床试验， 患有前列腺癌的人类患者。

Conventional prostate cancer therapies sometimes fail to provide satisfactory treatment results, while the side effects often significantly degrade patient quality of life. A more localized cancer treatment modality with minimal side effects is desired for the management of prostate cancer. Photodynamic therapy (PDT) utilizes locally delivered light energy to activate a pre-administered photosensitizer, which ultimately leads to controlled destruction of target tissue. Our objective, thus, is to develop PDT as an alternative/adjunctive therapy for prostate cancer by total prostate ablation. The specific aims are: (1) to optimize the PDT treatment schedules in prostate employing both the Dunning tumor model in rat and both normal and pre-irradiated canine prostate, (2) to determine the PDT damage threshold produced by varying photosensitizer and light doses, (3) to develop a treatment planning and monitoring technique using multi-purpose optical probes for accurate prostate ablation, and (4) to validate the procedures in an in vivo model for total prostate ablation. For the above investigations we propose to employ a unique second generation photosensitizer, Tookad, which acts primarily on local vasculature, and requires literally no waiting period between administration and light irradiation. This sensitizer has a rapid clearance from the body and is essentially cleared completely from all critical tissues within one day. We will qualitatively evaluate the photosensitizer pharmacokinetics. Optical probes will be used to measure dynamic light fluence distribution and tissue oxygenation during PDT. PDT induced lesions will be evaluated histopathologically and correlated to the treatment dosimetry for a damage threshold value. Similar procedures will be performed for adjacent structures. Based on the threshold values and information collected from the studies, we will develop treatment planning and monitoring techniques for our ultimate goal: total prostate ablation with minimal damage to adjacent structures. The procedures then will be tested in canine prostates pre-treated with ionizing radiation to simulate the conditions in patients who have failed conventional radiation therapy. The completion of the project will, thus, provide physicians with directly applicable information and techniques to plan clinical trials of PDT on human patients with prostate cancer.