COMPARATIVE BIODISTRIBUTION OF META-TETRA(HYDROXYPHENYL) CHLORIN IN MULTIPLE SPECIES - CLINICAL IMPLICATIONS FOR PHOTODYNAMIC THERAPY

Background and Objective: To optimize photodynamic therapy, it is nece ssary to know the distribution of photosensitizer in normal tissue as well as tumors and to know how well animal models match human. This st udy measured the biodistribution of meta-Tetra(Hydroxyphenyl) Chlorin (mTHPC) in three species of animals and in humans. Study Design/Materi als and Methods: mTHPC was injected intravenously into dogs, rabbits, rats, and humans, and drug levels in various tissues were determined 6 days later. One dog was perfused with 3 L of saline to remove blood t rapped within organs. Results: Absolute and relative concentrations of drug in specific tissues varied between species and between individua ls. There was a general pattern of distribution. Highly vascularized t issues had the highest levels of mTHPC, not simply due to trapping of blood. mTHPC did not localize in bone and did not cross the blood-brai n barrier. Humans had much higher levels of drug in their plasma and t issues than did animals. Conclusions: First, drug retention varies fro m one tissue to another. Second, there is significant variability from one individual to another, whether animal or human. Third, current mo dels cannot accurately predict from animal studies the optimum dose fo r humans. Measurement of photosensitizer level in plasma at time of tr eatment would allow optimal photodynamic dosing. (C) 1997 Wiley-Liss, Inc.