Pass H I, Evans S, Matthews W A, Perry R, Venzon D, Roth J A, Smith P
Thoracic Oncology Section, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
J Thorac Cardiovasc Surg. 1991 May;101(5):795-9.
Photodynamic therapy with dihematoporphyrin ether sensitizes malignant cells to damage by 630 nm light. The in vitro, in vivo photodynamic therapy sensitivity of a cell line transformed by the Kirsten ras oncogene (45342) was studied to establish a new photodynamic therapy model. With the colony formation assay, neither light alone nor dihematoporphyrin ether alone affected 45342 survival. Energy-dependent photodynamic therapy effects were seen in vitro in dihematoporphyrin ether-incubated and light-exposed cells (90% cytotoxicity = 950 joules/m2; 99% cytotoxicity = 1575 joules/m2; p2 less than 0.05). Subcutaneous allografts of 45342 were established in nu/nu mice, and ideal route (intravenous or intraperitoneal) of dihematoporphyrin ether delivery, dihematoporphyrin ether tissue kinetics, and in vivo photodynamic therapy effects were examined. Intravenous administration not only gave higher levels of the sensitizer in various tissues, but also was associated with less variation than the intraperitoneal route. Selective dihematoporphyrin ether retention was documented in the tumors at 24 hours after injection compared with other tissues, and photodynamic therapy with 0.3 W/cm2 to a total dose of 150 joules/cm2 led to progressive coagulative tumor necrosis and tumor regression. These studies confirm that transformed, malignant cells are sensitive to photodynamic therapy, and this model may prove in future studies to increase efficacy to photodynamic therapy (i.e., with dihematoporphyrin ether delivery by monoclonal antibodies).
用双血卟啉醚进行的光动力疗法可使恶性细胞对630nm光的损伤敏感。研究了由 Kirsten ras 癌基因转化的细胞系（45342）的体外和体内光动力疗法敏感性，以建立一种新的光动力疗法模型。通过集落形成试验，单独的光或单独的双血卟啉醚均不影响45342细胞的存活。在体外，在经双血卟啉醚孵育并暴露于光的细胞中观察到能量依赖性光动力疗法效应（90%细胞毒性 = 950焦耳/平方米；99%细胞毒性 = 1575焦耳/平方米；p2小于0.05）。在裸鼠中建立了45342细胞的皮下同种异体移植模型，并研究了双血卟啉醚给药的理想途径（静脉内或腹腔内）、双血卟啉醚的组织动力学以及体内光动力疗法效应。静脉内给药不仅在各种组织中产生更高水平的敏化剂，而且与腹腔内途径相比变化更小。与其他组织相比，注射后24小时在肿瘤中记录到双血卟啉醚的选择性潴留，用0.3W/cm²至总剂量150焦耳/cm²进行光动力疗法导致肿瘤进行性凝固性坏死和肿瘤消退。这些研究证实，转化的恶性细胞对光动力疗法敏感，并且该模型可能在未来的研究中证明可提高光动力疗法的疗效（即通过单克隆抗体递送双血卟啉醚）。
