Laser-induced fluorescence endoscopy (LIFE) during photodynamic therapy (PDT) for esophageal cancer Academic Article uri icon

abstract

  • Purpose: The purpose of this study was to measure photosensitizer (PS) levels in normal and malignant esophageal tissue before and after palliative PDT in order to assess PS concentration and selectivity, and the effectiveness of PS activation by light (a potential predictor of cytotoxic substance generation and necro-inflammatory response). Methods: Four esophageal cancer patients scheduled for palliative PDT were given 1 to 2 mg/kg IV Photofrin®. PDT was performed 6 h after the 1 mg/kg dose and 48-72 h after the 2 mg/kg dose. Immediately before PDT real-time LIFE images, point spectroscopy and standard mucosal biopsies were taken from 2 sites in normal and 3 sites in malignant mucosa. At least 5 spectra were collected from each interrogated mucosal site, detected with an optical multichannel analyzer, and normalized to 750 nm during data analysis. Biopsies obtained from the same sites were processed for subsequent ex situ fluorescence quantification by chemical extraction. The tumor was then exposed to 630 nm light from an argon dye laser (delivered via a cylindrical diffusing tip) for a total light dose of 300 J/cm. Immediately after PDT, LIFE images, point spectroscopy, and biopsies were again taken from normal and malignant sites. This sequence was repeated 48 hours later at the time of a second application of laser light. Results: Real-time LIFE images after delivery of each light dose showed a marked decrease in fluorescence intensity in malignant (compared with normal) areas suggesting photobleaching and potential PS photoactivation. Tissue extraction data [average μg/g/dose ±SD]: Specific Uptake Ratio Pre-PDT1 Post-PDT1 Pre-PDT2 Post-PDT2 Normal 1.30 ± 0.40 1.37 ± 0.39 1.41 ± 0.38 1.69 ± 0.60 Tumor 3.09 ± 2.30 3.14 ± 1.43 5.29 ± 6.16 2.39 ± 1.40 showed a 2.5-fold greater PS selectivity for tumor and a large variability in porphyrin concentration. Analysis of the area under the spectral curves confirmed the extraction results. Conclusions: PS levels accumulate selectively in malignant esophageal mucosa compared to normal mucosa. After PDT, tissue PS measurement by spectroscopy and chemical extraction may be influenced by endogenous porphyrin generation or intratumor oxygenation or uptake variability. However, real-time LIF endoscopy detects a qualitative decrease in malignant tissue fluorescence levels indicating photochemical activation of the PS and, indirectly, the degree of photobiologic (cytotoxic) effect. LIFE may be a practical clinical adjunct for dosimetry in PDT.

publication date

  • January 1, 1997