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Protoporphyrin IX distribution following local application of 5-aminolevulinic acid and its esterified derivatives in the tissue layers of the normal rat colon.
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MedLine Citation:
PMID:  11720447     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Photodynamic diagnosis and especially therapy after sensitization with 5-aminolevulinic acid (ALA) is hampered by limitations of uptake and distribution of ALA due to its hydrophilic nature. Chemical modification of ALA into its more lipophilic esters seems to be promising to overcome these problems. The aim of the present study was to investigate the comparative kinetics of protoporphyrin IX (PPIX) fluorescence in rat colonic tissue after topical application of ALA and its esterified derivatives, ALA-hexylester (h-ALA), ALA-methylester (m-ALA) and ALA-benzylester (b-ALA). Fluorescence intensity induced by PPIX in normal colonic tissue was quantified using fluorescence microscopy at 1, 2, 4, 6 and 8 h after sensitization. Mucosa exhibited higher fluorescence levels compared to the underlying submucosa or smooth muscle. Peak fluorescence intensities were seen 4 h after local sensitization with 86.0 mol ml(-1) ALA (513 +/- 0.57 counts per pixel), 6.6 mol ml(-1) m-ALA (508 +/- 35.50) and 4.8 mol ml(-1) h-ALA (532 +/- 128.80), and 6 h after sensitization with 4.6 mol ml(-1) b-ALA (468 +/- 190.27). A 13-18 times lower concentration of ALA esters was required for fluorescence intensities reached with ALA alone. A similar degree of the fluorescence ratio between mucosa and muscularis (5-6:1) was detected for ALA and its derivatives. The time point of the maximum value of this ratio was consistent with peak fluorescence levels for ALA and each ALA-ester. The clinical feasibility and the advantages of topical ALA ester-based fluorescence for detection of malignant and premalignant lesions need further investigations.
Authors:
E Endlicher; P Rümmele; F Hausmann; R Krieg; R Knüchel; H C Rath; J Schölmerich; H Messmann
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of cancer     Volume:  85     ISSN:  0007-0920     ISO Abbreviation:  Br. J. Cancer     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-26     Completed Date:  2002-02-14     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  0370635     Medline TA:  Br J Cancer     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  1572-6     Citation Subset:  IM    
Affiliation:
Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.
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MeSH Terms
Descriptor/Qualifier:
Aminolevulinic Acid / administration & dosage,  analogs & derivatives*,  pharmacokinetics*
Animals
Colon / drug effects,  metabolism*
Female
Kinetics
Microscopy, Fluorescence
Photosensitizing Agents / administration & dosage,  pharmacokinetics*
Protoporphyrins / analysis*
Rats
Tissue Distribution
Chemical
Reg. No./Substance:
0/5-aminolevulinic acid hexyl ester; 0/Photosensitizing Agents; 0/Protoporphyrins; 0/delta-aminolevulinic acid methyl ester; 106-60-5/Aminolevulinic Acid; 553-12-8/protoporphyrin IX
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Full Text
Journal Information
Journal ID (nlm-ta): Br J Cancer
ISSN: 0007-0920
ISSN: 1532-1827
Publisher: Nature Publishing Group
Article Information
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Copyright 2001, Cancer Research Campaign
Received Day: 20 Month: 02 Year: 2001
Revision Received Day: 25 Month: 06 Year: 2001
Accepted Day: 19 Month: 07 Year: 2001
Print publication date: Month: 11 Year: 2001
Volume: 85 Issue: 10
First Page: 1572 Last Page: 1576
ID: 2363929
Publisher Item Identifier: 6692124
DOI: 10.1054/bjoc.2001.2124
PubMed Id: 11720447

Protoporphyrin IX distribution following local application of 5-aminolevulinic acid and its esterified derivatives in the tissue layers of the normal rat colon
E Endlicher1
P Rümmele2
F Hausmann3
R Krieg1
R Knüchel2
H C Rath1
J Schölmerich1
H Messmann1
1Department of Internal Medicine I, 2Institute of Pathology, 3Institute of Inorganic Chemistry, University of Regensburg, Regensburg, 93042, Germany
*Author for correspondence: helmut.messman@klinik.uni-regensburg.de


Article Categories:
  • Regular Article

Keywords: 5-aminolevulinic acid, 5-aminolevulinic esters, protoporphyrin IX, fluorescence, colon.

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