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

Abstract

The study aims to compare the standard/continuous light delivery with fractionated light delivery for interstitial photodynamic therapy (PDT) of prostate cancer. Dunning R3327 prostate tumor models were established in male syngeneic rats. When tumors reached approximately 3,000 mm3, 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. 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. 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.