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.
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.
Manivasager
Vanaja
V
Division of Medical Sciences, National Cancer Centre, Singapore 169610, Singapore.
Yee
Karen Kar Lye
KK
Heng
Paul Wan Sia
PW
Soo
Khee Chee
KC
Olivo
Malini
M
D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D002277:Carcinoma / Q000175:diagnosis*; D006801:Humans; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009303:Nasopharyngeal Neoplasms / Q000175:diagnosis*; D017319:Photosensitizing Agents / Q000008:administration & dosage*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000032:analysis* / Q000378:metabolism; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays
D017319:Photosensitizing Agents; D011524:Protoporphyrins; C114767:delta-aminolevulinic acid methyl ester; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; C041104:dimethyl protoporphyrin IX