Photodynamic therapy with phthalocyanine sensitisation: quantitative studies in a transplantable rat fibrosarcoma.
Photodynamic therapy with phthalocyanine sensitisation: quantitative studies in a transplantable rat fibrosarcoma.
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DOI：
10.1038/bjc.1987.78
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发表时间：
1987-04
影响因子：
8.8
通讯作者：
Bown, S G
中科院分区：
文献类型：
--
作者：
Tralau, C J;MacRobert, A J;Coleridge-Smith, P D;Barr, H;Bown, S G
光动力疗法（PDT）是一种有前途的方法，局部破坏恶性肿瘤，但很少有工作已经做，以确定哪些因素控制的程度，组织坏死产生。使用一种新的光敏剂，磺化铝酞菁（AlSPc）和光从氩离子泵浦染料激光在675 nm，我们量化的影响，间质PDT在大鼠可移植纤维肉瘤。在100 mW激光功率下，热效应与PDT相当，因此随后的研究在50 mW下进行，其中热效应最小。PDT坏死深度随能量的对数增加而增加。AlSPc的组织浓度通过碱提取测量，并且在敏化后的所有时间，与给定光剂量产生的坏死良好相关。与肌肉中3小时的峰值相比，在敏化后24-48小时出现AlSPc的峰值肿瘤浓度。24 h肿瘤：肌肉的峰值比为2：1。除了不同的时间间隔，以达到峰值敏化剂浓度，肿瘤损伤的程度与光和敏化剂的参数以类似的方式在正常肝脏中发现，虽然在肿瘤中的光学穿透深度更大（2.5毫米与1.8毫米）。在剂量低于1毫克kg-1的AlSPc坏死的直径增加的致敏剂的剂量的对数，从0.25到0.5毫克kg-1的剂量增加一倍，坏死的深度增加了50%。然而，在较高剂量下，变化较小，并且对于相同的光剂量，将剂量从2.5 mg kg-1增加至5 mg kg-1仅使坏死增加10%。在所有剂量范围内，AlSPc的组织浓度的给定百分比增加对于相同的光剂量给出了坏死程度的小得多的百分比增加，这表明肿瘤和正常组织之间坏死的选择性可能远小于光敏剂保留的选择性。根据这些结果，如果已知光剂量、AlSPc的组织浓度和组织的光穿透深度，则该纤维肉瘤中PDT坏死的程度与正常肝脏中的情况一样可预测。现在需要对不同的肿瘤模型进行进一步的研究，以确定当肿瘤在其起源器官中生长时，而不是在本研究中使用可移植肿瘤的非生理情况下，肿瘤与相邻正常组织相比如何反应。
Photodynamic therapy (PDT) is a promising approach to the local destruction of malignant tumours, but little work has been done to determine which factors control the extent of tissue necrosis produced. Using a new photosensitiser, a sulphonated aluminium phthalocyanine (AlSPc) and light from an argon ion pumped dye laser at 675 nm, we quantified the effects of interstitial PDT in a transplantable fibrosarcoma in rats. At 100mW laser power, thermal effects were comparable to those of PDT, so subsequent studies were carried out at 50 mW, where thermal effects were minimal. The depth of PDT necrosis increased with the logarithm of the applied energy. Tissue concentration of AlSPc was measured by alkali extraction and at all times after sensitisation, correlated well with the necrosis produced with a given light dose. Peak tumour concentration of AlSPc occurred 24-48 h after sensitisation compared with a peak at 3 h in muscle. The peak ratio tumour:muscle was 2:1 at 24 h. Apart from a different time interval to reach the peak sensitiser concentration, the extent of tumour damage varied with the light and sensitiser parameters in a similar way to that found in normal liver, although the optical penetration depth was greater in the tumour (2.5 mm vs. 1.8 mm). At doses of AlSPc below 1 mg kg-1 the diameter of necrosis increased with the logarithm of the dose of sensitiser, and doubling the dose from 0.25 to 0.5 mg kg-1 increased the depth of necrosis by 50%. However, at higher doses, the changes were smaller and increasing the dose from 2.5 to 5 mg kg-1 only increased the necrosis by 10% for the same light dose. In all dose ranges, a given percentage increase in the tissue concentration of AlSPc gave a much smaller percentage increase in the extent of necrosis for the same light dose, suggesting that selectivity of necrosis between tumour and normal tissue is likely to be much less than the selectivity of retention of the photosensitiser. From these results, the extent of PDT necrosis in this fibrosarcoma is as predictable as it is in normal liver if the light dose, tissue concentration of AlSPc and optical penetration depth of the tissue are known. Further studies are now required on different tumour models to establish how tumours respond compared with adjacent normal tissue when the tumour is growing in its organ of origin rather than the non-physiological situation using a transplantable tumour as in this study.