Protoporphyrin IX-accumulation in human tumor cells following topical ALA- and h-ALA-application in vivo

Zenzen, Volker; Zankl, Heinrich

doi:10.1016/j.canlet.2003.07.001

Cited by 22 publications

(14 citation statements)

References 16 publications

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“…[5,6] PpIX preferentially accumulates in tumor cells resulting in the downregulation of PpIX to heme, [7,8] and, thus, is applicable to PDD and PDT as a photosensitizer. [9] ALA-induced PDD allows simultaneous visualization and treatment of malignant glioma, superficial bladder cancer, and other neoplastic diseases.…”

Section: Introductionmentioning

confidence: 99%

Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy

Ishizuka

Abe

Sano

et al. 2011

International Immunopharmacology

227

218

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Section: Introductionmentioning

confidence: 99%

Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy

Ishizuka

Abe

Sano

et al. 2011

International Immunopharmacology

227

218

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“…Red versus blue light illumination in hexyl 5- [3][4][5] and cellular uptake [6][7][8] compared to ALA. Following conversion of HAL to ALA by cellular esterases, the molecule enters the heme synthesis pathway and induces increased intracellular levels of the photosensitizer protoporphyrin IX (PpIX), the direct precursor of heme.…”

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confidence: 99%

Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcomein vitro

et al. 2014

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Abstract. Hexyl 5-aminolevulinate (HAL) is a lipophilic derivative of 5-aminolevulinate, a key intermediate in biosynthesis of the photosensitizer protoporphyrin IX (PpIX). The photodynamic efficacy and cell death mode after red versus blue light illumination of HAL-induced PpIX have been examined and compared using five different cancer cell lines. LED arrays emitting at 410 and 624 nm served as homogenous and adjustable light sources. Our results show that the response after HAL-PDT is cell line specific, both regarding the shape of the dose-survival curve, the overall dose required for efficient cell killing, and the relative amount of apoptosis. The ratio between 410 and 624 nm in absorption coefficient correlates well with the difference in cell killing at the same wavelengths. In general, the PDT efficacy was several folds higher for blue light as compared with red light, as expected. However, HAL-PDT 624 induced more apoptosis than HAL-PDT 410 and illumination with low irradiance resulted in more apoptosis than high irradiance at the same lethal dose. This indicates differences in death modes after low and high irradiance after similar total light doses. From a treatment perspective, these differences may be important. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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“…Subsequently this tumour cell line was xenografted on the flanks of Balb/c nude mice to study the uptake and retention kinetics in an in vivo system. There have been several studies using ester derivatives of 5-ALA (19)(20)(21)(22) namely hexyl-ester for PDT and PDD based on the rationale that esters are transported into cells at a faster rate. Up to date no extensive studies have been conducted using exogenous PpIX and its ester derivative PME in PDT or PDD of cancer cells.…”

Section: Discussionmentioning

confidence: 99%

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

Manivasager

Yee²,

Heng³

et al. 2006

Int J Oncol

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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.

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Protoporphyrin IX-accumulation in human tumor cells following topical ALA- and h-ALA-application in vivo

Cited by 22 publications

References 16 publications

Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy

Novel development of 5-aminolevurinic acid (ALA) in cancer diagnoses and therapy

Red versus blue light illumination in hexyl 5-aminolevulinate photodynamic therapy: the influence of light color and irradiance on the treatment outcomein vitro

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

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