Effects of TOOKAD-PDT on Canine Prostates Pre-Treated with Ionizing Raidiation

摘要

PDT in prostate cancer will likely be implemented clinically with patients who have failed prior ionizing radiation therapy (RT). The current study is to develop an in vivo model to evaluate the effects of PDT on prostatic tissue after RT. To produce a physiological and anatomical environment in prostate similar to that in patients who have failed RT, canine prostates (n = 4) were subjected to a definitive course of ionizing radiation therapy (2.7 Gy X 20 fractions)5 to 6 months prior to PDT. A laparotomy was performed to expose the prostate for PDT. Second generation photosensitizer Tookad (Palladium-Bacteriopheophorbide, Steba Biotech, The Netherlands) acts primarily on tissue vasculature and is very effective in destroying normal prostatic tissue, as shown by our prior studies. Due to the extremely fast clearance of the photosensitizer, interstitial light irradiation (760 nm, 50-200 J/cm, 150 mW/cm from a 1 cm diffuser fiber) was delivered 4 minutes after the onset of Tookad infusion (i.v. 2.5 mg/ml, 2 mg/kg, total infusion time 10 min). The prostates were harvested for histopathology one week after PDT. At one week, the lesions were characterized by acute hemorrhagic necrosis with patchy sub-capsular hyperemia and edema. The maximum lesion diameter for 50, 100 and 200 J/cm PDT was approximately 15, 20 and 28 mm, respectively. The lesion size is well correlated with light fluence and comparable to that in prostats treated with identical PDT doses but without prior-RT. Under light-microscopy, the PDT induced necrosis is clearly distinguishable from the radiation induced fibrosis. No urethral lesions were observed. Dyer's Verthoeff stain showed the loss of stromal connective tissue and the acinar collagen in the PDT treated area. There was no noticeable damage on the bladder or underlying colon section. In conclusion, Tookad-PDT can effectively destroy prostate tissue with prior-RT induced fibrosis, thus, may provide an alternative modality for those prostate-cancer patients who have failed RT.