A study of 5-aminolevulinic acid and its methyl ester used in in vitro and in vivo systems of human bladder cancer.
The use of 5-aminolevulinic acid and its esters to induce endogenous porphyrins for the purpose of detection of epithelial cancers is being studied extensively in many centres around the world. The challenge is to prepare an efficacious formulation for the purpose of cancer detection. Photodynamic diagnosis of cancer using 5-aminolevulinic acid (ALA) and its ester derivatives is being actively investigated. In this study, we compared ALA with ALA methyl ester (AME) derivative in terms of PpIX fluorescence intensity in in vitro and in vivo systems of bladder carcinoma. For the in vivo system consisting of RT112 xenografts, the modes of drug administration compared were intravenous administration and topical application. The Karl Storz fluorescence endoscopy system was used to obtain macroscopic fluorescence images. The macroscopic images were further analysed for fluorescence intensity distribution. For the intravenous administration, over all time points studied (1, 3, 6 h), AME-PpIX fluorescence was lower than ALA-PpIX fluorescence and was cleared at a faster rate than the ALA-PpIX when administered intravenously. Topical application with two different polymers, Gantrez and Polyvinyl pyrrolidone (PVP) which are fast releasing polymers was found to be comparable in inducing PpIX fluorescence. Topical AME-PpIX fluorescence was found to be comparable with ALA-PpIX fluorescence. The results of this study suggest that the AME can also be used as a good diagnostic agent.
Manivasager
Vanaja
V
Division of Medical Sciences, National Cancer Centre, Singapore 169610.
Heng
Paul Wan Sia
PW
Hao
Jinsong
J
Zheng
Wei
W
Soo
Khee Chee
KC
Olivo
Malini
M
D000287:Administration, Topical; D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active; D002277:Carcinoma / Q000175:diagnosis* / Q000473:pathology; D003558:Cystoscopy; D005294:Ferrochelatase / Q000378:metabolism; D006801:Humans; D011163:Hydroxymethylbilane Synthase / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000378:metabolism; D017319:Photosensitizing Agents / Q000032:analysis; D011524:Protoporphyrins / Q000032:analysis* / Q000096:biosynthesis; D013050:Spectrometry, Fluorescence; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000737:chemistry*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000473:pathology
D009363:Neoplasm Proteins; D017319:Photosensitizing Agents; D011524:Protoporphyrins; C114767:delta-aminolevulinic acid methyl ester; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX; D011163:Hydroxymethylbilane Synthase; D005294:Ferrochelatase