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Fluence rate as a modulator of PDT mechanisms
Author(s) -
Henderson Barbara W.,
Busch Theresa M.,
Snyder John W.
Publication year - 2006
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.20327
Subject(s) - fluence , photodynamic therapy , biophysics , irradiation , oxygen , chemistry , cancer research , biology , physics , organic chemistry , nuclear physics
Background and Objectives Molecular oxygen in the tissue to be treated by photodynamic therapy (PDT) is critical for photodynamic cell killing. The fluence rate of PDT light delivery has been identified as an important modulator of tissue oxygenation and treatment outcome. This article provides supporting evidence for the role of fluence rate in PDT and discusses the underlying mechanisms. Study Design/Materials and Methods Intratumoral pO 2 was measured polarographically in murine tumors before and during PDT light treatment using the Eppendorf pO 2 Histograph. Tumor response as a function of fluence rate and fluence was also assessed in murine tumor models. Changes in vascular permeability as a function of fluence rate were determined in murine tumors by measuring tumor uptake of fluorescent beads (200 nm diameter). Results Severe oxygen depletion is shown to occur within seconds of illumination at a fluence rate of 75 mW/cm 2 in radiation‐induced fibrosarcoma (RIF) tumors photosensitized with AlPcS 2 . This effect was reversible and consistent with photochemical oxygen depletion, which has been shown by us and others to be fluence rate dependent. It is demonstrated that fluence rate affects the PDT tumor response in the Colon 26 tumor model, high fluence rate diminishing or even totally inhibiting tumor control, low fluence rate promoting tumor control. The influence of fluence rate is not restricted to cytocidal effects, but can also be seen in sublethal conditions such as vascular permeability. Conclusions Fluence rate of PDT light delivery exerts far‐reaching control upon treatment outcome through its oxygenation modulating properties and possibly other mechanisms yet to be identified. This has been shown to be true in the preclinical and clinical setting. Further development of in situ dosimetry will be necessary to take full advantage of these discoveries. Lasers Surg. Med. © 2006 Wiley‐Liss, Inc.