The kinetics of protoporphyrin IX (PPIX) synthesis, bioconversion to other metabolic products, and photobleaching were measured in cell cultures after incubation in media containing the metabolic precursor for heme synthesis, \delta -aminolevulinic acid (5 ALA). A compartmental model described the kinetics in terms of rate constants for the three processes. The maximum amount of PPIX that can be attained in the cells and the concentration of 5 ALA in the medium that obtains this maximum were determined. Using this information, two dosimetry protocols are outlined which both involve complete photobleaching of the PPIX: (1) the classical acute protocol using maximum 5 ALA to produce maximum PPIX and a light treatment of about 0.5-1 hr, and (2) a novel prolonged protocol using continuous low-level 5 ALA delivery to produce only slightly elevated PPIX and an extended light exposure time of over 24 hrs.
S. L. Jacques, X. He, G. Gofstein, "Design of PDT protocols using \delta -aminolevulinic acid (5ALA)," SPIE Proceedings of Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy II, edited by T. J. Dougherty, 1881, 99-108 (1993).