Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies

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The aim of this work was to test in vitro and in vivo the efficacy of the derivatives of 5-aminolevulinic acid (ALA): hexyl-ALA (He-ALA), undecanoyl-ALA and R,S-2-(hydroximethyl)tetrahydropyranyl-ALA (THP-ALA) as pro-photosensitising agents. The compounds were assayed in a cell line derived from a m...

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Autores principales:	Perotti, C., Fukuda, H., DiVenosa, G., MacRobert, A.J., Batlle, A., Casas, A.
Formato:	Artículo publishedVersion
Lenguaje:	Inglés
Publicado:	2004
Materias:	ALA ALA derivatives Aminolevulinic acid PDT Photodynamic therapy 2 (hydroxymethyl)tetrahydropyranyl 5 aminolevulinic acid aminolevulinic acid hexyl 5 aminolevulinic acid photosensitizing agent porphyrin unclassified drug undecanoyl 5 aminolevulinic acid drug derivative animal cell animal experiment animal model animal tissue article bioaccumulation breast tumor cell line controlled study correlation analysis drug determination drug efficacy drug uptake explant ion exchange chromatography male mouse nonhuman photodynamic therapy phototoxicity porphyrin metabolism priority journal animal Bagg albino mouse biosynthesis chemistry experimental neoplasm methodology photochemotherapy Aminolevulinic Acid Animals Male Mammary Neoplasms, Animal Mice Mice, Inbred BALB C Photochemotherapy Photosensitizing Agents Porphyrins
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_00070920_v90_n8_p1660_Perotti
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

id	paperaa:paper_00070920_v90_n8_p1660_Perotti
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spelling	paperaa:paper_00070920_v90_n8_p1660_Perotti2023-06-12T16:41:21Z Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies Br. J. Cancer 2004;90(8):1660-1665 Perotti, C. Fukuda, H. DiVenosa, G. MacRobert, A.J. Batlle, A. Casas, A. ALA ALA derivatives Aminolevulinic acid PDT Photodynamic therapy 2 (hydroxymethyl)tetrahydropyranyl 5 aminolevulinic acid aminolevulinic acid hexyl 5 aminolevulinic acid photosensitizing agent porphyrin unclassified drug undecanoyl 5 aminolevulinic acid aminolevulinic acid drug derivative photosensitizing agent porphyrin animal cell animal experiment animal model animal tissue article bioaccumulation breast tumor cell line controlled study correlation analysis drug determination drug efficacy drug uptake explant ion exchange chromatography male mouse nonhuman photodynamic therapy phototoxicity porphyrin metabolism priority journal animal Bagg albino mouse biosynthesis chemistry experimental neoplasm methodology photochemotherapy Aminolevulinic Acid Animals Male Mammary Neoplasms, Animal Mice Mice, Inbred BALB C Photochemotherapy Photosensitizing Agents Porphyrins The aim of this work was to test in vitro and in vivo the efficacy of the derivatives of 5-aminolevulinic acid (ALA): hexyl-ALA (He-ALA), undecanoyl-ALA and R,S-2-(hydroximethyl)tetrahydropyranyl-ALA (THP-ALA) as pro-photosensitising agents. The compounds were assayed in a cell line derived from a murine mammary tumour, in tumour explants and after injection of the cells into mice. In vitro, undecanoyl-ALA and THP-ALA did not improve ALA efficacy in terms of porphyrin synthesis. On the other hand, half of the amount of ALA is required to obtain the same plateau amount of photosensitiser from He-ALA. However, this plateau value cannot be surpassed in spite of the four-times higher accumulation of ALA/He-ALA from the ALA derivative. This shows that He-ALA conversion to porphyrins but not He-ALA entry to the cells is limiting. Employing ionic exchange chromatography, we found that 80% of total uptake was He-ALA whereas only 20% was ALA. This suggests that the esterases, probably themselves regulated by the heme pathway, are limiting the conversion of ALA derivatives into porphyrins. A similar situation occurs with THP-ALA. Tumour explant porphyrin results correlate well with cell line data. However, i.p. injection of ALA derivatives to mice resulted in a lower porphyrin concentration in the tumour when compared to the administration of equimolar amounts of ALA, indicating that there should be retention of ALA derivatives either within the blood vessels in the initial phase of distribution and/or within the capillaries of the tumour. © 2004 Cancer Research UK. Fil:Perotti, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Fukuda, H. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Batlle, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Casas, A. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 2004 info:eu-repo/semantics/article info:ar-repo/semantics/artículo info:eu-repo/semantics/publishedVersion application/pdf eng info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00070920_v90_n8_p1660_Perotti
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
language	Inglés
orig_language_str_mv	eng
topic	ALA ALA derivatives Aminolevulinic acid PDT Photodynamic therapy 2 (hydroxymethyl)tetrahydropyranyl 5 aminolevulinic acid aminolevulinic acid hexyl 5 aminolevulinic acid photosensitizing agent porphyrin unclassified drug undecanoyl 5 aminolevulinic acid aminolevulinic acid drug derivative photosensitizing agent porphyrin animal cell animal experiment animal model animal tissue article bioaccumulation breast tumor cell line controlled study correlation analysis drug determination drug efficacy drug uptake explant ion exchange chromatography male mouse nonhuman photodynamic therapy phototoxicity porphyrin metabolism priority journal animal Bagg albino mouse biosynthesis chemistry experimental neoplasm methodology photochemotherapy Aminolevulinic Acid Animals Male Mammary Neoplasms, Animal Mice Mice, Inbred BALB C Photochemotherapy Photosensitizing Agents Porphyrins
spellingShingle	ALA ALA derivatives Aminolevulinic acid PDT Photodynamic therapy 2 (hydroxymethyl)tetrahydropyranyl 5 aminolevulinic acid aminolevulinic acid hexyl 5 aminolevulinic acid photosensitizing agent porphyrin unclassified drug undecanoyl 5 aminolevulinic acid aminolevulinic acid drug derivative photosensitizing agent porphyrin animal cell animal experiment animal model animal tissue article bioaccumulation breast tumor cell line controlled study correlation analysis drug determination drug efficacy drug uptake explant ion exchange chromatography male mouse nonhuman photodynamic therapy phototoxicity porphyrin metabolism priority journal animal Bagg albino mouse biosynthesis chemistry experimental neoplasm methodology photochemotherapy Aminolevulinic Acid Animals Male Mammary Neoplasms, Animal Mice Mice, Inbred BALB C Photochemotherapy Photosensitizing Agents Porphyrins Perotti, C. Fukuda, H. DiVenosa, G. MacRobert, A.J. Batlle, A. Casas, A. Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies
topic_facet	ALA ALA derivatives Aminolevulinic acid PDT Photodynamic therapy 2 (hydroxymethyl)tetrahydropyranyl 5 aminolevulinic acid aminolevulinic acid hexyl 5 aminolevulinic acid photosensitizing agent porphyrin unclassified drug undecanoyl 5 aminolevulinic acid aminolevulinic acid drug derivative photosensitizing agent porphyrin animal cell animal experiment animal model animal tissue article bioaccumulation breast tumor cell line controlled study correlation analysis drug determination drug efficacy drug uptake explant ion exchange chromatography male mouse nonhuman photodynamic therapy phototoxicity porphyrin metabolism priority journal animal Bagg albino mouse biosynthesis chemistry experimental neoplasm methodology photochemotherapy Aminolevulinic Acid Animals Male Mammary Neoplasms, Animal Mice Mice, Inbred BALB C Photochemotherapy Photosensitizing Agents Porphyrins
description	The aim of this work was to test in vitro and in vivo the efficacy of the derivatives of 5-aminolevulinic acid (ALA): hexyl-ALA (He-ALA), undecanoyl-ALA and R,S-2-(hydroximethyl)tetrahydropyranyl-ALA (THP-ALA) as pro-photosensitising agents. The compounds were assayed in a cell line derived from a murine mammary tumour, in tumour explants and after injection of the cells into mice. In vitro, undecanoyl-ALA and THP-ALA did not improve ALA efficacy in terms of porphyrin synthesis. On the other hand, half of the amount of ALA is required to obtain the same plateau amount of photosensitiser from He-ALA. However, this plateau value cannot be surpassed in spite of the four-times higher accumulation of ALA/He-ALA from the ALA derivative. This shows that He-ALA conversion to porphyrins but not He-ALA entry to the cells is limiting. Employing ionic exchange chromatography, we found that 80% of total uptake was He-ALA whereas only 20% was ALA. This suggests that the esterases, probably themselves regulated by the heme pathway, are limiting the conversion of ALA derivatives into porphyrins. A similar situation occurs with THP-ALA. Tumour explant porphyrin results correlate well with cell line data. However, i.p. injection of ALA derivatives to mice resulted in a lower porphyrin concentration in the tumour when compared to the administration of equimolar amounts of ALA, indicating that there should be retention of ALA derivatives either within the blood vessels in the initial phase of distribution and/or within the capillaries of the tumour. © 2004 Cancer Research UK.
format	Artículo Artículo publishedVersion
author	Perotti, C. Fukuda, H. DiVenosa, G. MacRobert, A.J. Batlle, A. Casas, A.
author_facet	Perotti, C. Fukuda, H. DiVenosa, G. MacRobert, A.J. Batlle, A. Casas, A.
author_sort	Perotti, C.
title	Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies
title_short	Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies
title_full	Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies
title_fullStr	Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies
title_full_unstemmed	Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies
title_sort	porphyrin synthesis from ala derivatives for photodynamic therapy. in vitro and in vivo studies
publishDate	2004
url	http://hdl.handle.net/20.500.12110/paper_00070920_v90_n8_p1660_Perotti
work_keys_str_mv	AT perottic porphyrinsynthesisfromaladerivativesforphotodynamictherapyinvitroandinvivostudies AT fukudah porphyrinsynthesisfromaladerivativesforphotodynamictherapyinvitroandinvivostudies AT divenosag porphyrinsynthesisfromaladerivativesforphotodynamictherapyinvitroandinvivostudies AT macrobertaj porphyrinsynthesisfromaladerivativesforphotodynamictherapyinvitroandinvivostudies AT batllea porphyrinsynthesisfromaladerivativesforphotodynamictherapyinvitroandinvivostudies AT casasa porphyrinsynthesisfromaladerivativesforphotodynamictherapyinvitroandinvivostudies
_version_	1769810154958618624

Porphyrin synthesis from ALA derivatives for photodynamic therapy. In vitro and in vivo studies

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