Document Detail

Enhancement of delta aminolevulinic acid-photodynamic therapy in vivo by decreasing tumor pH with glucose and amiloride.
MedLine Citation:
PMID:  11802027     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES/HYPOTHESIS: Delta aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) is a fluorescent sensitizer that permits detection and treatment of squamous cell carcinoma of the oral cavity. An exogenously induced decrease in tissue pH was evaluated for its effect in enhancing cellular uptake of ALA and facilitating its transformation into PpIX. STUDY DESIGN: Mice grafted with HT29 colonic cancers had been given glucose and amiloride to modify the pH of tissues. Influence of pH changes has been evaluated on ALA-induced PPIX fluorescence by optic fiber spectrofluorimetry as well as on tumor growth. METHODS: RESULTS: The pH in HT 29 tumor decreased from 7.1 to 6.67 (P < .05) after intraperitoneal injection of glucose and amiloride. The PpIX fluorescence ratios in tumor or muscle before, between, and 2 hours after glucose and amiloride injection were not higher than control ratios. Aminolevulinic acid-photodynamic therapy was more efficient on HT 29 tumor-bearing mice when the pH value was decreased with glucose and amiloride, showing a difference in the tumor growth index ratio from the 1st to 14th day of 22% between amiloride-glucose aminolevulinic acid-photodynamic therapy and aminolevulinic acid-photodynamic therapy alone (P < .05). CONCLUSIONS: Glucose and amiloride did not change PpIX fluorescence in HT 29 tumor after intraperitoneal injection of aminolevulinic acid but enhanced aminolevulinic acid-photodynamic therapy efficacy. This was probably a result of mechanisms other than an increase in aminolevulinic acid cellular penetration and PpIX production, such as susceptibility to free radical toxicity or alteration of cellular repair enzymes under acidotic conditions. If a decrease of pH induces a more efficient photodynamic therapy as suggested by our results, an easier way to obtain this decrease than glucose and amiloride would be necessary for clinical applications.
B Piot; N Rousset; P Lenz; S Eléouet; J Carré; V Vonarx; L Bourré; T Patrice
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  The Laryngoscope     Volume:  111     ISSN:  0023-852X     ISO Abbreviation:  Laryngoscope     Publication Date:  2001 Dec 
Date Detail:
Created Date:  2002-01-21     Completed Date:  2002-02-07     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8607378     Medline TA:  Laryngoscope     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2205-13     Citation Subset:  IM    
Laboratoire de Photobiologie des Cancers, Centre Hospitalier Régional et Universitaire de Nantes, Nantes, France.
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MeSH Terms
Acid-Base Equilibrium / drug effects*
Adenocarcinoma / pathology*
Amiloride / pharmacology*
Aminolevulinic Acid / pharmacology*
Colonic Neoplasms / pathology*
HT29 Cells
Hydrogen-Ion Concentration
Neoplasm Transplantation
Protoporphyrins / pharmacokinetics
Reg. No./Substance:
0/Protoporphyrins; 106-60-5/Aminolevulinic Acid; 2609-46-3/Amiloride

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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