Document Type

Article

Publication Date

10-14-2017

Publication Title

Photodiagnosis and Photodynamic Therapy

Department

Thayer School of Engineering

Additional Department

Geisel School of Medicine

Abstract

Background

Sunlight can activate photodynamic therapy (PDT), and this is a proven strategy to reduce pain caused by conventional PDT treatment, but assessment of this and other alternative low dose rate light sources, and their efficacy, has not been studied in an objective, controlled pre-clinical setting. This study used three objective assays to assess the efficacy of different PDT treatment regimens, using PpIX fluorescence as a photophysical measure, STAT3 cross-linking as a photochemical measure, and keratinocyte damage as a photobiological measure.

Methods

Nude mouse skin was used along with in vivo measures of photosensitizer fluorescence, keratinocyte nucleus damage from pathology, and STAT3 cross-linking from Western blot analysis. Light sources compared included a low fluence rate red LED panel, compact fluorescent bulbs, halogen bulbs and direct sunlight, as compared to traditional PDT delivery with conventional and fractionated high fluence rate red LED light delivery.

Results

Of the three biomarkers, two had strong correlation to the PpIX-weighted light dose, which is calculated as the product of the treatment light dose (J/cm2) and the normalized PpIX absorption spectra. Comparison of STAT3 cross-linking to PpIX-weighted light dose had an R = 0.74, and comparison of keratinocyte nuclear damage R = 0.70. There was little correlation to PpIX fluorescence. These assays indicate most of the low fluence rate treatment modalities were as effective as conventional PDT, while fractionated PDT showed the most damage.

Conclusions

Daylight or artificial light PDT provides an alternative schedule for delivery of drug-light treatment, and this pre-clinical assay demonstrated that in vivo assays of damage could be used to objectively predict a clinical outcome in this altered delivery process.

Graphical abstract

Low-fluence daylight photodynamic therapy (PDT) has been shown to reduce pain with similar efficacy of conventional treatments. Three objective assays were performed to assess efficacy of different light treatment strategies: PpIX photobleaching, STAT3 crosslinking, and keratinocyte damage. Of these metrics, STAT3 crosslinking and keratinocyte damage showed a strong correlation to the PpIX-weighted light dose.

DOI

10.1016/j.pdpdt.2017.10.005

Comments

This work is licensed under a CC BY NC ND 4.0 license.

Original Citation

de Souza ALR, LaRochelle E, Marra K, Gunn J, Davis SC, Samkoe KS, Chapman MS, Maytin EV, Hasan T, Pogue BW. Assessing daylight & low-dose rate photodynamic therapy efficacy, using biomarkers of photophysical, biochemical and biological damage metrics in situ. Photodiagnosis Photodyn Ther. 2017 Dec;20:227-233. doi: 10.1016/j.pdpdt.2017.10.005. Epub 2017 Oct 14. PMID: 29037911; PMCID: PMC5718943.

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