Comparative biodistribution of meta-Tetra (Hydroxyphenyl) chlorin in multiple species: Clinical implications for photodynamic therapy

Abstract

BACKGROUND AND OBJECTIVE: To optimize photodynamic therapy, it is necessary to know the distribution of photosensitizer in normal tissue as well as tumors and to know how well animal models match human. This study measured the biodistribution of meta-Tetra(Hydroxyphenyl) Chlorin (mTHPC) in three species of animals and in humans. STUDY DESIGN/MATERIALS AND METHODS: mTHPC was injected intravenously into dogs, rabbits, 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 trapped within organs. RESULTS: Absolute and relative concentrations of drug in specific tissues varied between species and between individuals. There was a general pattern of distribution. Highly vascularized tissues 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-brain barrier. Humans had much higher levels of drug in their plasma and tissues than did animals. CONCLUSIONS: First, drug retention varies from one tissue to another. Second, there is significant variability from one individual to another, whether animal or human. Third, current models cannot accurately predict from animal studies the optimum dose for humans. Measurement of photosensitizer level in plasma at time of treatment would allow optimal photodynamic dosing.