Ris H B, Giger A, Hof V I, Mettler D, Stewart J C, Althaus U, Altermatt H J
Department of Thoracic and Cardiovascular Surgery, University of Bern, Inselspital, Switzerland.
Eur J Cardiothorac Surg. 1997 Oct;12(4):542-8. doi: 10.1016/s1010-7940(97)00191-7.
Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on intrathoracic tissues of minipigs with the same drug-light conditions to optimise the antitumour activity of PDT while preventing photosensitising injury to normal tissues.
Laser light (20 J/cm2) at 652 nm was delivered to the xenografts 1-4 days after i.p. administration of 0.1 mg/kg m-tetrahydroxyphenyl-chlorin (mTHPC) or an equimolar dose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respectively. The extent of tumour necrosis was assessed by histomorphometry. Intraoperative PDT was then performed to the thoracic cavity of minipigs through a sternotomy with the same drug-light conditions at drug-light intervals ranging from 12 h to 6 days after i.v. administration of mTHPC and pegylated mTHPC, respectively.
Both, mTHPC and pegylated mTHPC, resulted in photosensitised necrosis of mesothelioma xenografts at drug-light intervals from 1 to 4 days but the extent of necrosis was significantly larger by use of pegylated mTHPC instead of mTHPC at a drug-light interval of 3 and 4 days. The optimal tumourcidal effect was achieved with pegylated mTHPC at a drug-light interval of 4 days. The photosensitising effect of mTHPC on intrathoracic tissues of minipigs revealed severe damage of virtually all tissues except nerves at short drug-light intervals. Tissue damage gradually became less at longer drug-light intervals and was absent at intervals of 3 days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed.
PDT with pegylated mTHPC reveals the potential of selective tumour destruction in this experimental setting and deserves further evaluation for intraoperative application in patients with malignant mesothelioma.
在荷人恶性间皮瘤异种移植瘤的裸鼠以及处于相同药物 - 光照条件下的小型猪的胸腔组织上，评估使用两种二氢卟吩敏化剂的光动力疗法（PDT），以优化PDT的抗肿瘤活性，同时防止对正常组织的光致敏损伤。
分别在腹腔注射0.1 mg/kg间 - 四羟基苯基二氢卟吩（mTHPC）或等摩尔剂量的聚乙二醇衍生的mTHPC（聚乙二醇化mTHPC）后1 - 4天，将652 nm的激光（20 J/cm²）照射到异种移植瘤上。通过组织形态计量学评估肿瘤坏死程度。然后在小型猪的胸腔内进行术中PDT，通过胸骨切开术，在静脉注射mTHPC和聚乙二醇化mTHPC后分别在12小时至6天的药物 - 光照间隔下保持相同的药物 - 光照条件。
mTHPC和聚乙二醇化mTHPC在1至4天的药物 - 光照间隔下均导致间皮瘤异种移植瘤的光致敏坏死，但在3天和4天的药物 - 光照间隔下，使用聚乙二醇化mTHPC而非mTHPC时坏死程度明显更大。在4天的药物 - 光照间隔下，聚乙二醇化mTHPC实现了最佳的杀肿瘤效果。mTHPC对小型猪胸腔组织的光致敏作用显示，在短药物 - 光照间隔下，除神经外几乎所有组织均受到严重损伤。在较长的药物 - 光照间隔下，组织损伤逐渐减轻，在3天及更长的间隔时无损伤。相比之下，在评估的任何药物 - 光照间隔下，聚乙二醇化mTHPC对任何结构均未产生明显变化。
在本实验环境中，聚乙二醇化mTHPC的PDT显示出选择性肿瘤破坏的潜力，值得进一步评估其在恶性间皮瘤患者术中的应用。
