Irradiation-induced enhancement of Pc 4 fluorescence and changes in light scattering are potential dosimeters for Pc 4-PDT.

Abstract:

:Phthalocyanine 4 (Pc 4) is a promising photosensitizer currently in clinical trials. Photobiological responses to Pc 4 photodynamic therapy (Pc 4-PDT) have been characterized extensively, but relatively little has been done to evaluate dose metrics for this sensitizer. We describe an irradiation-induced increase in fluorescence in tumor cell monolayers. This increase is due solely to enhanced fluorescence from Pc 4, as confirmed by confocal spectroscopy. In EMT6 cells incubated with 250 nM Pc 4 for 24 h, the maximum increase in fluorescence is approximately 3.7-fold above baseline levels. This increase occurs over a range of fluences, 0.05-0.6 J cm(-2), where clonogenic survival decreases by 3 orders of magnitude. Light scattering measurements performed on similarly treated EMT6 cells in suspension suggested a Pc 4-PDT-mediated mitochondrial swelling of approximately 13% at 0.6 J cm(-2), where fluorescence enhancement saturates under these treatment conditions. Fluorescence imaging and light scattering experiments performed at a five-fold lower Pc 4 incubation concentration revealed a reduced fluorescence enhancement at a five-fold higher fluence, which produced comparable mitochondrial swelling. Taken together, these data suggest that Pc 4 is initially aggregated at high local concentration in mitochondria and that irradiation relaxes the quenching of Pc 4 fluorescence through a mechanism that may involve mitochondrial swelling.

journal_name

Photochem Photobiol

authors

Wang KK,Wilson JD,Kenney ME,Mitra S,Foster TH

doi

10.1111/j.1751-1097.2007.00128.x

subject

Has Abstract

pub_date

2007-09-01 00:00:00

pages

1056-62

issue

5

eissn

0031-8655

issn

1751-1097

pii

PHP128

journal_volume

83

pub_type

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