Fluence rate as a modulator of PDT mechanisms

Lasers in Surgery and Medicine
Barbara W HendersonJohn W Snyder

Abstract

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. Intratumoral pO2 was measured polarographically in murine tumors before and during PDT light treatment using the Eppendorf pO2 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). Severe oxygen depletion is shown to occur within seconds of illumination at a fluence rate of 75 mW/cm2 in radiation-induced fibrosarcoma (RIF) tumors photosensitized with AlPcS2. 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...Continue Reading

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