Determination of the maximal tumor:normal bladder ratio after i.p. or bladder administration of 5-aminolevulinic acid in Fischer 344 rats by fluorescence spectroscopy in situ.

The two major steps in our study on the treatment of bladder tumors by photodynamic therapy (PDT) were the development of a new bladder tumor model in Fischer rats by implantation of tumor cells and the use of fluorescence spectroscopy, a semi-quantitative and non-invasive method, in order to determine the time after general or local administration of a photosensitizer when the tumor:normal bladder ratio was at its highest. 5-Aminolevulinic acid (5-ALA) (250 mg/kg body weight) was injected i.p. or instilled directly into the bladder cavity for 1, 2 or 4 h and fluorescence was measured on normal and bladder tumor tissues every 30 min for 8-10 h after administration, with a special miniaturized optical-fiber captor. The better tumor:normal bladder ratios were 2.85+/-1.2 at 3.5 h after i.p. administration and 3.96+/-1.04 after bladder instillation for 4 h, respectively. These results were confirmed by fluorescence microscopy. PDT with the same dose of 5-ALA as in this pharmacokinetic study must also be carried out in order to compare the toxicity of the two administration routes of the photosensitizer and to determine which one is the better for this bladder tumor model.

Induction of syngeneic intradermal and orthotopic epidermal carcinomas in hairless Skh-1 mice as a reproducible model for experiments.

Epidermoid carcinomas, clinically and histologically similar to human squamous cell carcinomas (SCC), were obtained in hairless Skh-1 mice. Tumor cells originated from chemically-induced skin cancers. We developed three models of orthotopic skin tumors: (1) intradermal injection of a tumor cell suspension, (2) superficial abrasion of the skin, cell grafting and application of a hydrocolloid dressing, (3) skin incision, seeding and application of a hydrocolloid dressing. Intradermal injection was 100% successful. Skin incision, displaying histological evidence of rapid invasive tumor growth, was 75% successful. Though skin tumor growth after abrasion was only 20% successful, the tumor histogenesis exactly imitated human SCC development. These carcinomas provide research models for further experiments such as photodynamic therapy or antiangiogenesis therapy.