Enhancement of Delta Aminolevulinic Acid–Photodynamic Therapy In Vivo by Decreasing Tumor pH With Glucose and Amiloride

Abstract

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.

Influence of CO2pneumoperitoneum on intracellular pH and signal transduction in cancer cells

“…The need of cancer cells large amount of energy when they are in mitosis, cannot be satisfied by cancer cell's anaerobic metabolism and acidosis makes metabolic enzyme pH far away form the optimum pHi. So many cells will go into apoptosis (Piot et al, 2001).…”

Effects of tumour acidification with glucose+MIBG on the spontaneous metastatic potential of two murine cell lines

“…Current evidence suggests that the tumour microenvironmental characteristic, acidic pH e , can be exploited and enhanced to Tumour acidification and metastasis T Kalliomäki and RP Hill improve the efficacy of hyperthermia, certain forms of chemotherapy and photodynamic therapy (Wike-Hooley et al, 1984;Tannock and Rotin, 1989;Jahde et al, 1992;Kuin et al, 1994Kuin et al, , 1999Kozin et al, 2001;Ohtsubo et al, 2001;Piot et al, 2001). However, acidic pH and lactate have also been associated with enhanced metastatic tumour progression both in experimental models (Schlappack et al, 1991;Jang and Hill, 1997) and clinically (Parkins et al, 1997;Walenta et al, 2000;Brizel et al, 2001).…”

“…Acidification of the tumour extracellular space with glucose alone or in combination with meta-iodo-benzylguanidine (MIBG) provides a means for preferential intracellular accumulation and enhanced cytotoxicity of weakly acidic chemotherapeutic drugs, such as chlorambucil (Kuin et al, 1999;Kozin et al, 2001) and increases tumour cell sensitivity to hyperthermia (Ohtsubo et al, 2001). Acidification of human colonic xenografts has also been shown to enhance their sensitivity to aminolevulinic acid-mediated photodynamic therapy (Piot et al, 2001).…”

Photodynamic therapy of virus-associated epithelial tumours of the face in organ transplant recipients

“…In this respect, SCCs appear similar in their PDT response to other carcinoma types, such as diverse (Corti et al 1995), colon carcinoma (Piot et al 2001), and bladder carcinoma (Shackley et al 2002). ALA-PDT in these tumours is subject to both experimental and clinical investigation (Biel 2002).…”