Enhancement of delta aminolevulinic acid-photodynamic therapy in vivo by decreasing tumor pH with glucose and amiloride

Objectives/Hypothesis. Delta aminolevulinic acid (ALA)-induced protoporphyr in IX (PpIX) is a fluorescent sensitizer that permits detection and treatme nt of squamous cell carcinoma of the oral cavity. An exogenously induced de crease in tissue pH was evaluated for its effect in enhancing cellular upta ke of ALA and facilitating its transformation into PpIX. Study Design. Alic e 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 AL A-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 t o 6.67 (P < .05) after intraperitoneal injection of glucose and amiloride. The PpIX fluorescence ratios in tumor or muscle before, between, and 2 hour s after glucose and amiloride injection were not higher than control ratios . Aminolevulinic acid-photodynamic therapy was more efficient on HT 29 tumo r-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 d ay of 22% between amiloride-glucose aminolevulinic acid-photodynamic therap y and aminolevulinic acid-photodynamic therapy alone (P < .05). Conclusions : Glucose and amiloride did not change PpIX fluorescence in HT 29 tumor aft er intraperitoneal injection of aminolevulinic acid but enhanced aminolevul inic acid-photodynamic therapy efficacy. This was probably a result of mech anisms other than an increase in aminolevulinic acid cellular penetration a nd PpIX production, such as susceptibility to free radical toxicity or alte ration of cellular repair enzymes under acidotic conditions. If a decrease of pH induces a more efficient photodynamic therapy as suggested by our res ults, an easier way to obtain this decrease than glucose and amiloride woul d be necessary for clinical applications.