6 March 2006 Photosensitizer dosimetry controlled PDT treatment planning reduces inter-individual variability in response to PDT
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Abstract
Effective Photodynamic therapy (PDT) treatment depends on the amount of active photosensitizer and the delivered light in the targeting tissue. For the same PDT treatment protocol, variation in photosensitizer uptake between animals induces variation in the treatment response between animals. This variation can be compensated via control of delivered light dose through photodynamic dose escalation based on online dosimetry of photosensitizer in the animal. The subcutaneous MAT-LyLu Dunning prostate tumor model was used in this study. Photosensitizer BPD-MA uptake was quantified by multiple fluorescence micro-probe measurements at 3 hours after verteporfin administration. PDT irradiation was carried out after photosensitizer uptake measurement with a total light dose of 75 J/cm2 and a light dose rate of 50 mW/cm2. Therapeutic response of PDT treatments was evaluated by the tumor regrowth assay. Verteporfin uptake varied considerably among tumors (inter-tumor variation 56% standard deviation) and within a tumor (largest intra-tumor variation 64%). An inverse correlation was found between mean photosensitizer intensity and PDT treatment effectiveness (R2 = 37.3%, p < 0.005). In order to compensate individual PDT treatments, photodynamic doses were calculated on an individual animal basis, by matching the light delivered to provide an equal photosensitizer dose multiplied by light dose. This was completed for the lower-quartile, mean and upper-quartile of the photosensitizer distribution. The coefficient of variance in the surviving fraction decreased from 24.9% in non-compensated PDT (NC-PDT) treatments to 16.0%, 14.0% and 15.9% in groups compensated to the lower-quartile (CL-PDT), the median (CM-PDT) and the upper-quartile (CU-PDT), respectively. In terms of treatment efficacy, the CL-PDT group was significantly less effective compared with NC-PDT, CM-PDT and CU-PDT treatments (p < 0.005). No significant difference in effectiveness was observed between NC-PDT, CM-PDT and CU-PDT. The results indicate that by measuring the mean photosensitizer concentration prior to light treatment, and then adjusting the light dose appropriately, a more uniform treatment can be applied to different animals thereby reducing the inter-individual variation in the treatment outcome.
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Xiaodong Zhou, Xiaodong Zhou, Brian W. Pogue, Brian W. Pogue, Bin Chen, Bin Chen, Eugene Demidenko, Eugene Demidenko, Rohan Joshi, Rohan Joshi, Jack Hoopes, Jack Hoopes, Tayyaba Hasan, Tayyaba Hasan, } "Photosensitizer dosimetry controlled PDT treatment planning reduces inter-individual variability in response to PDT", Proc. SPIE 6139, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XV, 61390P (6 March 2006); doi: 10.1117/12.647439; https://doi.org/10.1117/12.647439
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