Protoporphyrin IX (
PpIX) is produced in cells via the
heme synthesis pathway, from the substrate
aminolevulinic acid (ALA), and can be used for
tumor detection, monitoring or
photodynamic therapy.
PpIX production varies considerably between
tumor cell types, and determining the cell types and methods to optimize production is a central issue in properly utilizing this drug. A panel of eight
cancer cell types was examined for
PpIX production capacity, including breast, prostate, and
brain cancer tumors, and the production varied up to 10-fold among cell types. A positive correlation was seen between mitochondrial content and naturally occurring
PpIX prior to ALA administration, but mitochondrial content did not correlate to the yield of
PpIX resulting from the addition of ALA. Interestingly, total cell size was positively correlated to the yield of
PpIX from ALA administration. Addition of an
iron chelator, 1,2-dimethyl-3-hydroxy-4-pyridone (L1) in combination with ALA allows the final step in the
heme synthesis pathway, conversion of
PpIX to
heme, to be delayed, thereby further increasing the yield of
PpIX. Those cell types that had the lowest ALA to
PpIX production without L1 showed the largest percentage increase in production with L1. The study indicates that use of L1 in
tumors with a lower innate production of
PpIX with ALA alone may be the most productive approach to this combined delivery.