Protoporphyrin IX fluorescence photobleaching increases with the use of fractionated irradiation in the esophagus

Abstract

Fluorescence measurements have been used to track the dosimetry of photodynamic therapy (PDT) for many years, and this approach can be especially important for treatments with aminolevulinic-acid-induced protoporphyrin IX (ALA-PpIX). PpIX photobleaches rapidly, and the bleaching is known to be oxygen dependent, and at the same time, fractionation or reduced irradiance treatments have been shown to significantly increase efficacy. Thus, in vivo measurement of either the bleaching rate and/or the total bleaching yield could be used to track the deposited dose in tissue and determine the optimal treatment plans. Fluorescence in rat esophagus and human Barrett's esophagus are measured during PDT in both continuous and fractionated light delivery treatment, and the bleaching is quantified. Reducing the optical irradiance from 50 to 25 mW/cm did not significantly alter photobleaching in rat esophagus, but fractionation of the light at 1-min on and off intervals did increase photobleaching up to 10% more (p value=0.02) and up to 25% more in the human Barrett's tissue (p value<0.001). While two different tissues and two different dosimetry systems are used, the data support the overall hypothesis that light fractionation in ALA-PpIX PDT esophageal treatments should have a beneficial effect on the total treatment effect.

Monitoring the accumulation and dissipation of the photosensitizer protoporphyrin IX during standard dermatological methyl-aminolevulinate photodynamic therapy utilizing non-invasive fluorescence imaging and quantification

“…Previous studies have shown the relationship between photobleaching of PpIX and cellular damage (22,25,33,39) and previous work within our group has linked changes in fluorescence intensity recorded with the non-invasive imaging system to clinical outcome (56). The greater the photobleaching of PpIX the greater the likelihood a complete clinical clearance of the lesion will occur.…”

“…A positive correlation has been previously demonstrated between PpIX photobleaching and cellular damage (22,25,32,33), indicating that the greater the level of photobleaching the more efficacious the PDT treatment. This finding indicated that greater PpIX accumulation increases the potential of the therapy as more PpIX is available for activation during irradiation.…”

Effect of an oxygen pressure injection (OPI) device on the oxygen saturation of patients during dermatological methyl aminolevulinate photodynamic therapy

“…Our previous studies using fluorescence imaging have indicated that AK, BD and sBCC undergo similar fluorescence changes during MAL-PDT [23]. A positive correlation between PpIX photobleaching and cellular damage, and hence clinical efficacy of the treatment has also been previously demonstrated [25][26][27][28][29]. Therefore, we hypothesized here that if oxygen saturation could be manipulated positively (increased) with the employment of the OPI device, a difference in the level of PpIX photobleaching (greater amount) may have been detected which would ultimately affect clinical outcome (improvement).…”

The effects of protoporphyrin IX-induced photodynamic therapy with and without iron chelation on human squamous carcinoma cells cultured under normoxic, hypoxic and hyperoxic conditions

“…A positive correlation between PpIX photobleaching and cellular damage has been previously reported [14][15][16][17] and it is therefore a good indicator of PDT effectiveness. The difference between the 'pre' and 'post' PpIX fluorescence readings can be attributed to PpIX photobleaching and so these measurements were quantified and compared as both the percentage of preirradiation PpIX levels bleached on irradiation as well as the absolute level of PpIX photobleaching in arbitrary units (Fig.…”