Factors influencing tumor response to photodynamic therapy sensitized by intratumor administration of methylene blue

Timothy M. Baran, Benjamin R. Giesselman, Rui Hu, Merrill A. Biel, Thomas H. Foster

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

Background and objectives: We examined tumor response to methylene blue (MB)-mediated photodynamic therapy (PDT) in a murine tumor model. The goal was to investigate the effects of drug-light interval (DLI), injection vehicle, and fluence on tumor destruction. Fluorescence and reflectance spectroscopy informed our understanding. Materials and methods: EMT6 tumor cells were implanted intradermally on the backs of female BALB/c mice and grown to ∼4-mm diameter. Mice were given a 35μl, single site, intratumor injection of 500μg/ml MB administered in either a water or a 5% ethanol-5% Cremophor-90% saline vehicle. PDT was begun either immediately or after a 1-hour DLI with a fluence rate of 60mW/cm2. Each animal received a fluence of 240 or 480J/cm2. Fluorescence and reflectance spectra were captured before and during irradiation. Results: A protocol consisting of the Cremophor-based vehicle, 0 DLI, and a fluence of 480J/cm2 was the most effective, with a 55% cure rate as measured by no evidence of tumor 90 days after PDT. Use of the water vehicle with this fluence and DLI reduced the cure rate to 20%. Reducing the fluence to 240J/cm2 similarly reduced treatment efficacy with 0 and 1-hour DLIs. Univariate Cox proportional hazards analysis identified increased fluence, 0 versus 1-hour DLI, and the Cremophor versus water vehicle as highly significant independent predictors of long term tumor control (P<0.01 in each case). Multivariate analysis with model selection revealed fluence and injection vehicle as the best predictors of survival hazards. Fluorescence spectroscopy in vivo showed that MB fluorescence decreased monotonically during a 2-hour dark interval but was restored by irradiation. Reflectance spectroscopy revealed that MB at this injected concentration attenuates the treatment beam significantly. Conclusion: Sensitizer delivery vehicle, drug-light interval, and fluence contribute significantly to the tumor response to MB-mediated PDT.

Original languageEnglish (US)
Pages (from-to)728-735
Number of pages8
JournalLasers in Surgery and Medicine
Volume42
Issue number8
DOIs
StatePublished - Oct 2010

Keywords

  • fluorescence spectroscopy
  • methylene blue
  • photodynamic therapy
  • reflectance spectroscopy

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