APPLICATION OF PHOTODYNAMIC THERAPY FOR ANIMAL TUMOR ; ADAPTATION AND EFFECTIVENESS

在这项研究中，我们使用了BPD-MA(苯并卟啉衍生物单酸环A)，它是第二代光敏剂，在大约690 nm的波长下具有快速的身体清除和强大的光吸收；该波长允许相当高的光穿透到组织中。对BPD-MA光动力疗法治疗动物肿瘤进行了基础和临床研究。体外实验表明，光动力疗法诱导细胞的光敏性依赖于多种因素。在体内，BPD-MA的抗血管生成PDT对肿瘤血管有明显的损伤作用，且与细胞靶向PDT相比具有更好的抗肿瘤效果。考虑到BPD-MA的药代动力学参数，使用BPD-MA的抗血管生成PDT可以在短时间内完成，并且可以重复进行，因为BPD-MA可以快速从组织中清除，从而表现出低蓄积。因此，使用BPD-MA的光动力疗法是治疗…的一种有效形式。最后，对19只犬头部肿瘤进行了BPD-MA抗血管生成光动力疗法的疗效评价。在开始静脉注射0.5 mg/kg BPD-MA后15分钟，用690 nm激光照射每个肿瘤。在PDT后随访1年以上的病例中，6只口腔肿瘤犬的中位生存期为423天(300~743天)，1年存活率为67%。在5只患鼻腔肿瘤的犬中，这一数值分别为533天(129-694天)和60%。治疗前后CT增强值有显著差异(p&lt；0.001)，分别为54.3±25.8Hounsfield单位(HU)(15只狗21次治疗)和5.5±5.7HU(11只狗18次治疗)。19种治疗有效的肿瘤的平均CT增强值为57.2HU，2种治疗无效的肿瘤的平均CT增强值为27.5HU。主要的副作用是PDT后1周内治疗区域周围出现一过性水肿，但不需要任何特殊的治疗。此外，使用BPD-MA的抗血管生成PDT可以重复进行，因为BPD-MA可以迅速从组织中清除，因此表现出低蓄积。抗血管生成PDT可能是治疗犬实体恶性肿瘤的一种有前途的方法，且不会产生任何严重的副作用。血管造影CT对筛选抗血管生成PDT病例和判断抗血管生成PDT后的疗效有一定价值。在临床应用研究中，由于BPD-MA在血液中的浓度迅速下降，故认为肿瘤的光照射必须在给药后短时间内完成。相反，使用BPD-MA进行抗血管生成PDT，由于BPD-MA清除快，在组织中蓄积低，可在短时间内完成且可重复进行。结论：抗血管生成PDT可有效治疗局部实体瘤，且无严重副作用。较少

In this study, we used BPD-MA (benzoporphyrin derivative monoacid ring A) which is a second generation photosensitizer with a rapid body clearance and strong light absorption at a wavelength of approximately 690 nm ; this wavelength allows considerably high light penetration into the tissue. Basic and clinical studies on photodynamic therapy using BPD-MA for the treatment of animal tumor were performed.In vitro, it was suggested that photosensitivity of cells induced by PDT was dependent on several factors. In vivo, antiangiogenic PDT using BPD-MA induced a significant tumor vascular damage and a superior antitumor effect comparing with cellular-targeting PDT. By considering the pharmacokinetic parameters of BPD-MA, antiangiogenic PDT using BPD-MA could be completed within a short time period and be performed repeatedly because BPD-MA can be rapidly cleared from the tissues, and hence, shows low accumulation. Therefore, PDT using BPD-MA is suggested to be an effective form of treatment … More for canine malignant solid tumors.Finally, the efficacy of antiangiogenic PDT using BPD-MA in 19 dogs with head tumors was assesse. Each tumor was irradiated with 690-nm laser light at 15 minutes after initiating the intravenous infusion of 0.5 mg/kg BPD-MA. In cases that were followed-up for more than 1 year after PDT, the median survival time of 6 dogs with oral tumors was found to be 423 days (range, 300-743 days) and a 1-year survival rate was observed in 67% of the dogs. In 5 dogs with nasal cavity tumors, the values were 533 days (range, 129-694 days) and 60%, respectively. The computed tomography (CT) enhancement values before and after PDT were significantly different (p < 0.001) and were 54.3 ± 25.8 Hounsfield units (HU) (21 treatments in 15 dogs) and 5.5 ± 5.7 HU (18 treatments in 11 dogs). The mean CT enhancement value of the tumors in which 19 treatments were effective was 57.2 HU and that for tumors in which 2 treatments were ineffective was 27.5 HU. The major side effect was temporary edema around the treated area for 1 week after PDT ; however, it did not require any specific treatment. Moreover, antiangiogenic PDT using BPD-MA can be performed repeatedly because BPD-MA is rapidly cleared from the tissues and hence shows low accumulation. Antiangiogenic PDT might be a promising method for treating canine solid malignant tumors without causing any serious side effects. Angiographic CT might play a useful role in selecting antiangiogenic PDT cases and in determining the therapeutic effect after antiangiogenic PDT.In clinical application study, it was thought that the light irradiation to the tumor must be finished at short times after the administration of BPD-MA because of the rapid decrease of the BPD-MA concentration in the blood. Conversely, antiangiogenic PDT using BPD-MA could be finished at short times and performed repeatedly because of BPD-MA rapid clearance and low accumulation in tissues.It is concluded that antiangiogenic PDT was effectively able to treat locally solid tumors without any serious side effects. Less