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Photodynamic therapy using a protoporphyrinogen oxidase inhibitor
V H Fingar1, T J Wieman, K S McMahon
1Division of Surgical Oncology, Henry Vogt Cancer Institute, University of Louisville, Kentucky 40292, USA. vhfing01@pdt.bcc.louisville.edu
Cancer Research
|October 23, 1997
Summary
Endogenously generated porphyrins show promise for photodynamic therapy (PDT). An inhibitor, FP-846, increased porphyrins in tumors, leading to significant tumor regression with minimal damage to healthy tissue.
Area of Science:
- Biochemistry
- Oncology
- Photodynamic Therapy
Background:
- Endogenous porphyrin production is an emerging alternative to exogenous photosensitizers in photodynamic therapy (PDT).
- 5-aminolevulinic acid (ALA) administration is a common method to induce porphyrin synthesis.
- Enzyme inhibitors of heme biosynthesis can also increase intracellular porphyrin accumulation.
Purpose of the Study:
- To investigate the efficacy of a protoporphyrinogen oxidase inhibitor, FP-846, in inducing endogenous porphyrin accumulation for PDT.
- To evaluate the anti-tumor effects of FP-846-mediated PDT on mammary tumors in mice.
Main Methods:
- DBA/2 mice with SMT-F mammary tumors were fed diets containing varying concentrations of FP-846 (0-4000 ppm).
- Tumors were treated with 602-670 nm light after inhibitor administration.
- Tumor regression and cure rates were assessed and compared to Photofrin treatment.
Main Results:
- FP-846 administration led to elevated intracellular protoporphyrin IX levels.
- Light treatment resulted in dose-dependent tumor regression, influenced by inhibitor concentration, duration, and light dose.
- Tumor cure rates of 23% were observed with 4000 ppm FP-846 and 300 J/cm2 light, comparable to 20% with Photofrin.
Conclusions:
- FP-846 effectively induces porphyrin accumulation for PDT, achieving significant tumor regression.
- This approach demonstrates efficacy comparable to conventional photosensitizers with reduced normal tissue damage.