Evaluation of Tookad-mediated photodynamic effect on peripheral nerve in a canine model

Photodynamic therapy (PDT) mediated with a novel vascular targeting photosensitizer pd-bacteriopheophorbide (Tookad) has been investigated as an alternative modality for the treatment of prostate cancer and other diseases. This study investigated, for the first time, the vascular photodynamic effects of Tookad-PDT on nerve tissues. We established an in situ canine model using the cutaneous branches of the saphenous nerve to evaluate the effect of Tookad-PDT secondary to vascular damage on compound-action potentials. With Tookad dose of 2 mg/kg, treatment with 50 J/cm2 induced little change in nerve conduction. However, treatment with 100 J/cm2 resulted in decreases in nerve conduction velocities, and treatment with 200 J/cm2 caused a total loss of nerve conduction. Vasculature surrounding the saphenous nerve appeared irritated. The nerve itself looked swollen and individual fibers were not as distinct as they were before PDT treatment. Epineurium had mild hemorrhage, leukocyte infiltration, fibroplasias and vascular hypertrophy. However, the nerve fascicles and nerve fibers were free of lesions. We also studied the effect of Tookad-PDT secondary to vascular damage on the pelvic nerve in the immediate vicinity of the prostate gland. The pelvic nerve and saphenous nerve showed different sensitivity and histopathological responses to Tookad-PDT. Degeneration nerve fibers and necrotic neurons were seen in the pelvic nerve at a dose level of 1 mg/kg and 50 J/cm2. Adjacent connective tissue showed areas of hemorrhage, fibrosis and inflammation. Our preliminary results suggest that possible side effects of interstitial PDT on prostate nerve tissues need to be further investigated.