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

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.

Optical touch pointer for fluorescence guided glioblastoma resection using 5‐aminolevulinic acid

“…The significances of these studies are that the measurements are objective and a relatively low dose of ALA (5 mg/kg) provokes detectable fluorescence peaks related to the malignant tumor tissue. This drug passes the leaky blood-brain barrier (BBB) in the tumor but not the intact BBB in normal brain tissue and is converted to the fluorescence marker PpIX in the malignant cells [11,12]. PpIX is a natural substance in the heme cycle which is rapidly eliminated from the body.…”

Inactivation ofPlasmodium falciparumby Photodynamic Excitation of Heme‐Cycle Intermediates Derived from δ‐Aminolevulinic Acid

“…Heme is formed by the addition of an atom of ferrous iron to the ring-shaped PPIX, by ferrochelatase [5]. In humans, the synthesis of heme is tightly regulated; in the presence of sufficient levels of heme, the synthesis of ALA by ALA synthase is inhibited by a complex negative-feedback mechanism [6,7].…”

Feasibility of UV and Blue LEDs for Skin Lesions Fluorescence Diagnosis

“…Most of the LEDs in table 2 are suitable for fluorescence excitation of induced PpIX [9]. However the blue ultra bright discrete led is inappropriate for this purpose.…”