Petras Juzenas^1,2, Vladimir Iani¹ and Johan Moan¹
 

1		Department of Biophysics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway petras.juzenas@labmed.uio.no
2		Laser Research Centre, Vilnius University, Sauletekio al.9 c.3, LT-2040 Vilnius, Lithuania

ABSTRACT

The influence of temperature and anaesthesia on the uptake and bioconversion of 5-aminolevulinic acid (ALA) and its methylester derivative (ALA-Me) were investigated in normal mouse skin by the means of fluorescence spectroscopy. A cream containing 20% of ALA or 20% of ALA-Me (wt./wt.) was topically applied on the skin. The amount of synthesized porphyrins in skin was determined by measurements of porphyrin fluorescence. Protoporphyrin IX (PpIX) was found to be the main fluorescent photosensitizer. The penetration of ALA and ALA-Me into the skin as well as the subsequent production of PpIX were found to be temperature dependent processes. Practically no PpIX was formed in the skin as long as the skin temperature was kept low (12-16^oC) during the 3 h period of ALA and ALA-Me application. After the skin was warmed up (27-34^oC) the profile of PpIX fluorescence kinetic followed that of control (30-36^oC) mice, but with lower intensity indicating reduced penetration and/or uptake of ALA and ALA-Me in cold skin. Warm skin (36-38^oC) produced significantly more PpIX than cold skin did (28-29^oC, slightly active mice) during continuous application of ALA. Low temperature (14-23^oC, sleeping mice) or continuous anaesthesia (22^oC, sleeping mouse) greatly reduced the conversion of ALA into PpIX. The ALA-induced PpIX fluorescence was also detected in remote sites initially untreated with ALA-cream, while ALA-Me-induced PpIX fluorescence was mainly localized in treated spot. Such difference in systemic action of topically applied ALA and ALA-Me was also observed in mice previously treated with ice. In conclusion, the conversion of ALA and ALA-Me into PpIX is significantly reduced in cold skin. During topical application of drug, the important physiological parameter such as skin temperature should be taken into account.

Keywords: 5-aminolevulinic acid (ALA); 5-aminolevulinic acid methylester (ALA-Me); Fluorescence kinetics; Skin temperature; Anaesthesia.

Abbreviations: ALA, 5-aminolevulinic acid; ALA-Me 5-aminolevulinic acid methylester; PAP, Photoactive porphyrins; PpIX, Protoporphyrin IX; PDT, Photodynamic therapy; rel. u., relative intensity units.
 

TITLE AND ABSTRACT

INTRODUCTION

MATERIALS AND METHODS

RESULTS AND DISCUSSION

REFERENCES