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Journal of Environmental Pathology, Toxicology and Oncology
Fator do impacto: 1.241 FI de cinco anos: 1.349 SJR: 0.356 SNIP: 0.613 CiteScore™: 1.61

ISSN Imprimir: 0731-8898
ISSN On-line: 2162-6537

Journal of Environmental Pathology, Toxicology and Oncology

DOI: 10.1615/JEnvironPatholToxicolOncol.v26.i2.40
pages 89-103

Biochemical Manipulation via Iron Chelation to Enhance Porphyrin Production from Porphyrin Precursors

Alison Curnow
Cornwall Dermatology Research, Peninsula Medical School, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall, UK TR1 3HD
Andrew Pye
Cornwall Dermatology Research, Peninsula Medical School, Knowledge Spa, Royal Cornwall Hospital, Truro, Cornwall, UK TR1 3HD

RESUMO

Topical protoporphyrin IX (PPIX) induced photodynamic therapy (PDT) of basal cell carcinoma (BCC) produces good clinical outcomes with excellent cosmesis as long as the disease remains superficial. Efficacy for nodular BCC, however, appears inferior to standard treatment unless repeat treatments are performed. Enhancement is therefore required and may be possible by employing iron chelating agents to temporarily increase PPIX accumulation above the levels normally obtained using aminolaevulinic acid (ALA) or the methyl ester of ALA (MAL) alone. In vitro studies investigated the efficacies of the novel iron chelator, CP94 (1,2-diethyl-3-hydroxypyridin-4-one hydrochloride), and the established iron chelator, desferrioxamine (DFO), at increasing PPIX fluorescence in cultured human lung fibroblasts and squamous carcinoma cells incubated with ALA/MAL. CP94 was found to produce greater PPIX fluorescence when administered with ALA/MAL than either congener could produce alone. CP94 was also found to be superior to DFO in the enhancement of PPIX fluorescence and could be employed to accumulate the same levels of PPIX within a shorter time period. Clinical utilization of CP94 to enhance ALA/MAL-PDT could potentially result in greater PPIX accumulation or alternatively could be employed to reduce the length of the required drug-light interval. Clinical investigation of this is currently underway.


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