Cellular determinants of PpIX production

The cellular levels of iron and ferrochelatase are important determinants of PpIX yield under exogenous ALA stimulation. The use of iron chelators is based on the relative inefficiency of ferrochelatase compared to other enzymes, which causes PpIX build-up when heme precursors are produced at an increased rate. In some cancer cell lines lower levels of ferrochelatase have been found than in normal cells and this may contribute to tumor selectivity in certain cancers [197]. In an attempt to further reduce or totally abrogate heme formation, exogenous chelating agents were used to remove iron. It was shown in vitro that iron chelation caused both increased PpIX formation and improved PDT efficacy and in vivo applications in animals and humans have confirmed the concept [191,198,199]. In lymphocytes that express the transferrin receptor (CD71), which is interpreted as an indication of low intracellular iron levels, higher PpIX concentrations were reached under ALA stimulation [200]. In addition, an analysis of iron availability at the molecular level 

ANNE C.E. MOOR, BERNHARD ORTEL AND TAYYABA HASAN 

---