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

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Abstract
When 5-aminolevulinic acid ( ALA ) is administered topically, intravenously or intraperitoneally to tumor-bearing animals or humans, tumor selective production of protoporphyrin IX ( PpIX ) is frequently observed. Several biophysical, biochemical and physiological factors explain this tumor selectivity, among which the most important ones seem to be: (1) a relatively high concentration of the rate-limiting enzyme porphobilinogen deaminase (PBGD) in tumors; (2) relatively low concentrations of ferrochelatase (FC) and iron in many tumors; (3) a slightly elevated tumor temperature, related to inflammation; and (4) a compromised barrier of the skin overlying tumors, leading to an increased penetration of ALA into tumors. All these factors are discussed in the present work and new data concerning the significance of the skin barrier and the tumor temperature are presented. It is shown that compromising the skin of mice by tape-stripping the stratum corneum leads to a strongly enhanced ALA penetration into the skin and even into the circulation. The skin overlying tumors (WiDr colon carcinoma tumors transplanted subcutaneously to mice) is also much more permeable to ALA than normal skin, even through no physical damage of the tumor skin can be seen. PpIX formation from ALA can be increased by increasing the temperature.