A study comparing endogenous protoporphyrin IX induced by 5-ALA and ALA-methyl ester with exogenous PpIX and PpIX dimethyl ester in photodynamic diagnosis of human nasopharyngeal carcinoma xenografts

Abstract

Abstract. 5-Aminolevulinic acid (5-ALA) and its esters have been under intense investigation to enhance the endogenous production of protoporphyrin IX (PpIX) in tumour cells for the purpose of photodynamic diagnosis. In this study we have investigated the use of exogenous PpIX and its dimethyl ester (PME) and compared the results with endogenous PpIX produced via 5-ALA and ALA methyl ester (AME) in poorly differentiated NPC/CNE-2 nasopharyngeal carcinoma cells in both in vivo and in vitro systems. All prodrugs and photosensitizers were administered to tumour bearing balb/c nude mice either intravenously or topically. In vitro results show that 5-ALA induced more PpIX fluorescence when compared with AME in NPC/CNE-2 cells and PME showed better uptake than PpIX. In vivo results show that exogenous PpIX and PME show promise as good candidates as photosensitizers for photodynamic diagnosis as they exhibit significant selectivity between tumour tissue and normal tissue at 3 h. Modification of delivery vehicle used for application of exogenous PpIX and PME could allow for rapid uptake; better selectivity and localization of the photosensitizer.

Efficacy of a methyl ester of 5-aminolevulinic acid in photodynamic therapy for ovarian cancers

“…Pharmacological studies have also demonstrated that it is more stable and penetrates deeply into the tissues due to its increased lipophilicity (Peng et al 2001). Compared to the parental ALA, Methyl-ALA has been shown to produce higher intracellular PpIX concentrations at lower doses of photosensitizer, resulting in a similar phototoxic eVect (Manivasager et al 2006). Thus, this treatment is more eYcient than PDT mediated by ALA alone.…”

Fluorescence diagnosis using 5-aminolevulinic acid in coloproctology/Fluoreszenz-Diagnostik in der Koloproktologie mittels 5-Aminolävulinsäure

“…This can be explained by the increased enzyme activity at the initial stages of heme synthesis as well as a lack of ferrochelatase, an enzyme which turns PpIX into the photoinactive heme [3,4] . This form of heme cannot be detected by fluorescence.…”

Predictors and Limitations of the Penetration Depth of Photodynamic Effects in the Rodent Brain

“…While PpIX production in tumors is commonly achieved by oral, topical or systemic administration of 5‐ALA , there has been a resurgence of interest in delivering exogenous PpIX. This is because the polar 5‐ALA has limited diffusion through cell membranes and high doses of 5‐ALA must be administered to reach clinically efficacious levels of PpIX . Using xenograft tumor models, Manivasager et al .…”