Non-homogeneous liver distribution of photosensitizer and its consequence for photodynamic therapy outcome.
BACKGROUND
Photodynamic therapy is mainly used for treatment of malignant lesions, and is based on selective location of a photosensitizer in the tumor tissue, followed by light at wavelengths matching the photosensitizer absorption spectrum. In molecular oxygen presence, reactive oxygen species are generated, inducing cells to die. One of the limitations of photodynamic therapy is the variability of photosensitizer concentration observed in systemically photosensitized tissues, mainly due to differences of the tissue architecture, cell lines, and pharmacokinetics. This study aim was to demonstrate the spatial distribution of a hematoporphyrin derivative, Photogem, in the healthy liver tissue of Wistar rats via fluorescence spectroscopy, and to understand its implications on photodynamic response.


METHODS
Fifteen male Wistar rats were intravenously photosensitized with 1.5mg/kg body weight of Photogem. Laser-induced fluorescence spectroscopy at 532 nm-excitation was performed on ex vivo liver slices. The influence of photosensitizer surface distribution detected by fluorescence and the induced depth of necrosis were investigated in five animals.


RESULTS
Photosensitizer distribution on rat liver showed to be greatly non-homogeneous. This may affect photodynamic therapy response as shown in the results of depth of necrosis.


CONCLUSIONS
As a consequence of these results, this study suggests that photosensitizer surface spatial distribution should be taken into account in photodynamic therapy dosimetry, as this will help to better predict clinical results.
Vollet-Filho
José Dirceu
JD
Instituto de Física de São Carlos, Universidade de São Paulo, Av Trabalhador São-carlense, 400, CEP 13566-590, São Carlos, SP, Brazil. josedirceu@ursa.ifsc.usp.br
Caracanhas
Mônica Andrioli
MA
Grecco
Clóvis
C
Ferreira
Juliana
J
Kurachi
Cristina
C
Bagnato
Vanderlei Salvador
VS
D000818:Animals; D006415:Hematoporphyrins / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009336:Necrosis; D017319:Photosensitizing Agents / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D013050:Spectrometry, Fluorescence
D006415:Hematoporphyrins; D017319:Photosensitizing Agents