Murrer L H, Hebeda K M, Marijnissen J P, Star W M
Department of Clinical Physics, Dr Daniel Den Hoed Cancer Centre, University Hospital Rotterdam, The Netherlands.
Br J Cancer. 1999 May;80(5-6):744-55. doi: 10.1038/sj.bjc.6690418.
The damage to normal pig bronchial mucosa caused by photodynamic therapy (PDT) using mTHPC and Photofrin as photosensitizers was evaluated. An endobronchial applicator was used to deliver the light with a linear diffuser and to measure the light fluence in situ. The applied fluences were varied, based on existing clinical protocols. A fluence finding experiment with short-term (1-2 days) response as an end point showed considerable damage to the mucosa with the use of Photofrin (fluences 50-275 J cm(-2), drug dose 2 mg kg(-1)) with oedema and blood vessel damage as most important features. In the short-term mTHPC experiment the damage found was slight (fluences 12.5-50 J cm(-2), drug dose 0.15 mg kg(-1)). For both sensitizers, atrophy and acute inflammation of the epithelium and the submucosal glands was observed. The damage was confined to the mucosa and submucosa leaving the cartilage intact. A long-term response experiment showed that fluences of 50 J cm(-2) for mTHPC and 65 J cm(-2) for Photofrin-treated animals caused damage that recovered within 14 days, with sporadic slight fibrosis and occasional inflammation of the submucosal glands. Limited data on the pharmacokinetics of mTHPC show that drug levels in the trachea are similar at 6 and 20 days post injection, indicating a broad time window for treatment. The importance of in situ light dosimetry was stressed by the inter-animal variations in fluence rate for comparable illumination conditions.
评估了使用mTHPC和卟吩姆钠作为光敏剂的光动力疗法（PDT）对正常猪支气管黏膜造成的损伤。使用支气管内施照器通过线性扩散器传输光线并原位测量光通量。根据现有的临床方案改变所施加的光通量。以短期（1 - 2天）反应为终点的光通量探索实验表明，使用卟吩姆钠（光通量50 - 275 J cm(-2)，药物剂量2 mg kg(-1)）时黏膜出现相当大的损伤，水肿和血管损伤是最重要的特征。在短期mTHPC实验中发现的损伤较轻（光通量12.5 - 50 J cm(-2)，药物剂量0.15 mg kg(-1)）。对于两种光敏剂，均观察到上皮和黏膜下腺的萎缩及急性炎症。损伤局限于黏膜和黏膜下层，软骨保持完整。一项长期反应实验表明，mTHPC处理组光通量为50 J cm(-2)以及卟吩姆钠处理组光通量为65 J cm(-2)时，动物所受损伤在14天内恢复，伴有散在的轻微纤维化和黏膜下腺偶尔的炎症。关于mTHPC药代动力学的有限数据表明，注射后6天和20天时气管中的药物水平相似，这表明治疗的时间窗较宽。在可比的光照条件下，动物间光通量率的差异强调了原位光剂量测定的重要性。
