Effects of Pd-bacteriopheophorbide (TOOKAD)-mediated photodynamic therapy on canine prostate pretreated with ionizing radiation.
The aim of this study was to evaluate the effects of photodynamic therapy (PDT) using a novel palladium bacteriopherophorbide photosensitizer TOOKAD (WST09) on canine prostate that had been pretreated with ionizing radiation. To produce a physiological and anatomical environment in canine prostate similar to that in patients for whom radiotherapy has failed, canine prostates (n = 4) were exposed to ionizing radiation (54 Gy) 5 to 6 months prior to interstitial TOOKAD-mediated PDT. Light irradiation (763 nm, 50-200 J/cm at 150 mW/cm from a 1-cm cylindrical diffusing fiber) was delivered during intravenous infusion of TOOKAD at 2 mg/kg over 10 min. Interstitial measurements of tissue oxygen profile (pO(2)) and of local light fluence rate were also measured. The prostates were harvested for histological examination 1 week after PDT. The baseline pO(2) of preirradiated prostate was in the range 10-44 mmHg. The changes in relative light fluence rate during PDT ranged from 12 to 43%. The acute lesions were characterized by hemorrhagic necrosis, clearly distinguishable from the radiotherapy-induced pre-existing fibrosis. The lesion size was correlated with light fluence and comparable to that in unirradiated prostate treated with a similar TOOKAD-PDT protocol. There was no noticeable damage to the urethra, bladder or adjacent colon. The preliminary results obtained from a small number of animals indicate that TOOKAD-PDT can effectively ablate prostate pretreated with ionizing radiation, and so it may provide an alternative modality for those prostate cancer patients for whom radiotherapy has failed.
Huang
Zheng
Z
HealthONE Alliance, Denver, Colorado 80203, USA. fwhetzel@aol.com
Chen
Qun
Q
Trncic
Nadira
N
LaRue
Susan M
SM
Brun
Pierre-Hervé
PH
Wilson
Brian C
BC
Shapiro
Howard
H
Hetzel
Fred W
FW
D000818:Animals; D001429:Bacteriochlorophylls / Q000494:pharmacology*; D003131:Combined Modality Therapy / Q000379:methods; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D008027:Light; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011467:Prostate / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D011829:Radiation Dosage; D011839:Radiation, Ionizing
D001429:Bacteriochlorophylls; D017319:Photosensitizing Agents; C456120:palladium-bacteriopheophorbide; D010100:Oxygen