On the basis for tumor selectivity in the 5-aminolevulinic acid-induced synthesis of protoporphyrin IX

When 5-aminolevulinic acid (ALA) is administered topically, intravenously o r intraperitoneally to tumor-bearing animals or humans, tumor selective pro duction of protoporphyrin IX (PpIX) is frequently observed. Several biophys ical, biochemical and physiological factors explain this tumor selectivity, among which the most important ones seem to be: (1) a relatively high conc entration of the rate-limiting enzyme porphobilinogen deaminase (PBGD) in t umors: (2) relatively low concentrations of ferrochelatase (FC) and iron in many tumors; (3) a slightly elevated tumor temperature, related to inflamm ation; and (4) a compromised barrier of the skin overlying tumors, leading to an increased penetration of ALA into tumors. All these factors are discu ssed in the present work and new data concerning the significance of the sk in barrier and the tumor temperature are presented. It is shown that compro mising the skin of mice by tape-stripping the stratum corneum leads to a st rongly enhanced ALA penetration into the skin and even into the circulation . The skin overlying tumors (WiDr colon carcinoma tumors transplanted subcu taneously to mice) is also much more permeable to ALA than normal skin, eve n through no physical damage of the tumor skin can be seen. PpIX formation from ALA can be increased by increasing the temperature. Copyright (C) 2001 John Wiley & Sons, Ltd.