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， 而副作用往往会显著降低患者的生活质量。一种更局限性的癌症 前列腺癌的治疗需要副作用最小的治疗方法。 光动力疗法(PDT)利用局部传递的光能激活预先给药的 光敏剂，最终导致目标组织的受控破坏。我们的目标是， 因此，发展光动力疗法作为全前列腺前列腺癌的替代/辅助治疗方法。 消融。具体目标是：(1)优化前列腺光动力疗法治疗方案 采用大鼠Dunning肿瘤模型和正常及照射前犬模型 前列腺，(2)测定不同光敏剂产生的PDT损伤阈值和 小剂量，(3)开发多用途的治疗计划和监测技术 用于准确的前列腺消融的光学探头，以及(4)在活体实验中验证该程序 全前列腺消融术模型。对于上述调查，我们建议聘请一名独特的 第二代光敏剂Tookad，主要作用于局部血管系统，以及 从字面上讲，在给药和光照之间没有等待期。这种增感剂 能迅速从体内清除，基本上完全清除了所有关键组织 一天之内。我们将定性评价光敏剂的药代动力学。光学 探头将用于测量动态光通量分布和组织氧合 光动力疗法。将对PDT引起的损害进行组织病理学评估，并与治疗相关 损伤阈值的剂量测定。类似的程序将对相邻的 结构。根据从研究中收集到的阈值和信息，我们将 为我们的最终目标：总前列腺制定治疗计划和监测技术 消融，对邻近结构的损害最小。然后，这些程序将在 经电离辐射预处理的犬前列腺模拟患者的情况 都没有通过常规的放射治疗。因此，该项目的完成将提供 医生拥有直接适用的信息和技术来计划光动力疗法的临床试验 人类前列腺癌患者。

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.