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Assessment of a sheep animal model to optimise photodynamic therapy in the oesophagus

✍ Scribed by Thomas M. Glanzmann; Matthieu P.E. Zellweger; François Borle; Ramiro Conde; Alexandre Radu; Jean-Pierre Ballini; Yves Jaquet; Raphaëlle Pilloud; Hubert van den Bergh; Philippe Monnier; Snezana Andrejevic-Blant; Georges A. Wagnières

Publisher
John Wiley and Sons
Year
2009
Tongue
English
Weight
273 KB
Volume
41
Category
Article
ISSN
0196-8092

No coin nor oath required. For personal study only.

✦ Synopsis

Abstract

Background and Objectives

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).

Materials and 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.

Conclusion

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. Lasers Surg. Med. 41:643–652, 2009. © 2009 Wiley‐Liss, Inc.

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