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Photodynamic Therapy for Malignant Mesothelioma: Preclinical Studies for Optimization of Treatment Protocols ¶
Author(s) -
Schouwink Hugo,
Ruevekamp Marjan,
Oppelaar Hugo,
Van Veen Robert,
Baas Paul,
Stewart Fiona A.
Publication year - 2001
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1562/0031-8655(2001)0730410ptfmmp2.0.co2
Subject(s) - photodynamic therapy , photosensitizer , fluence , mesothelioma , oxygen , carbogen , oxygenation , medicine , photosensitivity , chemistry , cancer research , nuclear medicine , photochemistry , materials science , laser , pathology , optoelectronics , optics , physics , organic chemistry
Effective photodynamic therapy (PDT) depends on the optimization of factors such as drug dose, drug–light interval, fluence rate and total light dose (or fluence). In addition sufficient oxygen has to be present for the photochemical reaction to occur. Oxygen deficits may arise during PDT if the photochemical reaction consumes oxygen more rapidly than it can be replenished, and this could limit the efficacy of PDT. In this study we investigated the influence of the drug–light interval, illumination‐fluence rate and total fluence on PDT efficacy for the photosensitizer meta ‐tetrahydroxyphenylchlorin ( m THPC). The effect of increasing the oxygenation status of tumors during PDT was also investigated. PDT response was assessed from tumor‐growth delay and from cures for human malignant mesothelioma xenografts grown in nude mice. Tumor‐bearing mice were injected intravenously with 0.15 or 0.3 mg·kg −1 m THPC, and after intervals of 24–120 h, the subcutaneous tumors were illuminated with laser light (652 nm) at fluence rates of 20, 100 or 200 mW·cm −2 . Tumor response was strongly dependent on the drug–light interval. Illumination at 24 h after photosensitization was always significantly more effective than illumination at 72 or 120 h. For a drug–light interval of 24 h the tumor response increased with total fluence, but for longer drug–light intervals even high total fluences failed to produce a significant delay in tumor regrowth. No fluence‐rate dependence of PDT response was demonstrated in these studies. Nicotinamide injection and carbogen breathing significantly increased tumor oxygenation and increased the tumor response for PDT schedules with illumination at 24 h after photosensitizer injection.