The effect of photodynamic therapy on a retinoblastoma-like tumour. An experimental in vitro and in vivo study on the potential use of photodynamic therapy in the treatment of retinoblastoma.
A retinoblastoma-like tumour has been established and characterized in terms of growth rates in vitro and in vivo, and by histopathology and chromosome analysis. Injected tumour cells grew regularly in the vitreous body with a blood supply from the retinal vessels. The tumour tissue was histopathologically similar to that of anaplastic human retinoblastomas. Almost all the cells had a triploid chromosome number and the DNA amount in tumours was stable, suggesting a stable tumour system without drift against more anaplastic degrees. Tumour cells plated in culture flasks were grown in colonies. Evaluation of the number of clonogenic cells in treated, relative to non-treated flasks reflected a quantitative treatment response. When the cells were injected into the eyes of young rats, solid tumors were formed which grew regularly until perforation of the globes. The tumours were suitable for assessment of therapeutic response in terms of local tumour control after treatment. Photodynamic therapy (PDT) of cancers, using hematoporphyrin derivatives (HPD) and visible light, is a therapeutic modality where HPD is administered 1-5 days before local light irradiation of the tumour. The combination of HPD, light energy and oxygen produces the cytotoxic agent singlet oxygen which only exists in its active state for a few milliseconds. Using this modality, it may be possible to obtain local tumour destruction in light-irradiated areas and avoid spreading of the cytotoxic agents to other organs. The effect of PDT with purified HPD (Photofrin II) and red light has been evaluated in the characterized retinoblastoma-like tumour in vivo and in vitro. The experiments demonstrated that Photofrin II and red light destroys cells in tissue culture flasks. Local control of intraocular retinoblastoma-like tumours was obtained in up to 33% of the animals following a single treatment. Adverse effects in the present model were corneal and conjunctival damage. Generally, the effect of PDT increased with larger Photofrin II doses, higher energy doses or a shorter time interval between drug administration and light irradiation. Damage to the cornea or conjunctiva limited the maximum tolerable treatment doses in the present model. The experiments suggests that PDT is a safer treatment with Photofrin II 2.5 mg/kg and a high light energy dose than with 10 mg/kg and an equivalent lower light energy dose. In tissue culture flasks, the cell inactivation did not depend on the light energy rate but only on the total delivered energy dose. The cells had a low capacity to repair sublethal damage.(ABSTRACT TRUNCATED AT 400 WORDS)
Winther
J B
JB
Department of Ophthalmology, Holstebro Centralsygehus, Denmark.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D003228:Conjunctiva / Q000187:drug effects; D003315:Cornea / Q000187:drug effects; D017323:Dihematoporphyrin Ether; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005134:Eye Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D006414:Hematoporphyrin Photoradiation; D006415:Hematoporphyrins / Q000627:therapeutic use*; D008920:Misonidazole / Q000627:therapeutic use; D010778:Photochemotherapy / Q000009:adverse effects; D051381:Rats; D011916:Rats, Inbred F344; D012175:Retinoblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D014407:Tumor Cells, Cultured
D006415:Hematoporphyrins; D008920:Misonidazole; D017323:Dihematoporphyrin Ether