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

Ken Kang Hsin Wang, Jeremy D. Wilson, Malcolm E. Kenney, Soumya Mitra, Thomas H. Foster

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1056-1062
Number of pages7
JournalPhotochemistry and Photobiology
Volume83
Issue number5
DOIs
StatePublished - Sep 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry

Fingerprint Dive into the research topics of 'Irradiation-induced enhancement of Pc 4 fluorescence and changes in light scattering are potential dosimeters for Pc 4-PDT'. Together they form a unique fingerprint.

Cite this