Assessment of a sheep animal model to optimise photodynamic therapy in the oesophagus.
OBJECTIVE
Precursor lesions of oesophagus adenocarcinoma constitute a clinical dilemma. Photodynamic therapy (PDT) is an effective treatment for this indication, but it is difficult to optimise without an appropriate animal model. For this reason, we assessed the sheep model for PDT in the oesophagus with the photosensitiser meta-(tetra-hydroxyphenyl) chlorin (mTHPC).


METHODS
Twelve sheep underwent intravenous mTHPC injection, blood sampling and fluorescence measurements. mTHPC's pharmacokinetics was measured in vivo and in plasma by fluorescence spectroscopy. Biopsies of sheep oesophagus were compared to corresponding human tissue, and the mTHPC's biodistribution was studied under fluorescence microscopy. Finally, the sheep oesophageal mucosa was irradiated, 4 days after mTHPC's injection.


RESULTS
Histologically, the sheep and human oesophagus were closely comparable, with the exception of additional fatty tissue in the sheep oesophagus. mTHPC's pharmacokinetics in sheep and human plasmas were similar, with a maximum of concentration in the sheep 10 hours after i.v. injection. mTHPC's pharmacokinetics in vivo reached its maximum after 30-50 hours, then decreased to background levels, as in humans under similar conditions. Two days after injection, mTHPC was mainly distributed in the lamina propria, followed by a penetration into the epithelium. The sheep and human tissue sensitivity to mTHPC PDT was similar.


CONCLUSIONS
In conclusion, this model showed many similarities with humans as to mTHPC's plasma and tissue pharmacokinetics, and for tissue PDT response, making it suitable to optimise oesophagus PDT.
Glanzmann
Thomas M
TM
Institute of Chemical Sciences and Engineering, Swiss Federal Institute of Technology (EPFL), CH-1015 Lausanne, Switzerland.
Zellweger
Matthieu P E
MP
Borle
François
F
Conde
Ramiro
R
Radu
Alexandre
A
Ballini
Jean-Pierre
JP
Jaquet
Yves
Y
Pilloud
Raphaëlle
R
van den Bergh
Hubert
H
Monnier
Philippe
P
Andrejevic-Blant
Snezana
S
Wagnières
Georges A
GA
D000818:Animals; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D004947:Esophagus / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects*; D006801:Humans; D008652:Mesoporphyrins / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D023421:Models, Animal; D009092:Mucous Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D012756:Sheep
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin