Pretreatment photosensitizer dosimetry reduces variation in tumor response.
OBJECTIVE
To compensate for photosensitizer uptake variation in photodynamic therapy (PDT), via control of delivered light dose through photodynamic dose calculation based on online dosimetry of photosensitizer in tissue before treatment.


METHODS
Photosensitizer verteporfin was quantified via multiple fluorescence microprobe measurements immediately before treatment. 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, median, and upper quartile of the photosensitizer distribution. PDT-induced tumor responses were evaluated by the tumor regrowth assay.


RESULTS
Verteporfin uptake varied considerably among tumors and within a tumor. The coefficient of variation in the surviving fraction was found significantly decreased in groups compensated to the lower quartile (CL-PDT), the median (CM-PDT), and the upper quartile (CU-PDT) of photosensitizer distribution. The CL-PDT group was significantly less effective compared with NC-PDT (Noncompensated PDT), CM-PDT, and CU-PDT treatments. No significant difference in effectiveness was observed between NC-PDT, CM-PDT, and CU-PDT treatment groups.


CONCLUSIONS
This research suggests that accurate quantification of tissue photosensitizer levels and subsequent adjustment of light dose will allow for reduced subject variation and improved treatment consistency.
Zhou
Xiaodong
X
Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
Pogue
Brian W
BW
Chen
Bin
B
Demidenko
Eugene
E
Joshi
Rohan
R
Hoopes
Jack
J
Hasan
Tayyaba
T
D000465:Algorithms; D000818:Animals; D004195:Disease Models, Animal; D005240:Feasibility Studies; D053685:Laser Therapy; D008297:Male; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000528:radiation effects; D011166:Porphyrins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000528:radiation effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011829:Radiation Dosage; D051381:Rats; D000077362:Verteporfin
D017319:Photosensitizing Agents; D011166:Porphyrins; D000077362:Verteporfin