Fractionated versus Standard Continuous Light Delivery in Interstitial Photodynamic Therapy of Dunning Prostate Carcinomas

Purpose: The study aims to compare the standard/continuous light delivery with fractionated light delivery for interstitial photodynamic therapy (PDT) of prostate cancer. Experimental Design: Dunning R3327 prostate tumor models were established in male syngeneic rats. When tumors reached ∼3,000 mm 3 , animals were randomized to various treatment groups. Three hours after QLT0074 injection, tumors were illuminated by 690-nm light delivered by a computer-controlled switch, which sequentially directed light to one of the seven optical fibers in cycles. For comparison, tumors were treated with continuous illumination. Tumors treated with light-only served as control. Dynamic contrast-enhanced magnetic resonance imaging was used to monitor tumor perfusion changes before and after PDT. Results: Tumor response (animal survival) to PDT with fractionated light delivery was PDT dose dependent in both tumor models. Rats bearing anaplastic tumor treated by fractionated light (PDT dose: 1.5 mg/kg QLT0074, 900 J light) had a median survival of 51 days with 25% tumor cures compared with that of 26 days with no tumor cure by continuous illumination ( P = 0.015) and 14 days by light-only ( P = 0.0001). Rats bearing well-differentiated tumor treated by fractionated light had a median survival of 82 days compared with 65 days by continuous illumination ( P = 0.001) and 37 days by light-only. PDT with fractionated light generated a perfusion reduction of 80% compared with 52% for continuous illumination in well-differentiated tumors. Conclusions: Fractionated light delivery is more effective than continuous light delivery in PDT of prostate cancer (solid tumors). These results warrant further investigation in clinical trials.