Tumor selectivity at short times following systemic administration of a liposomal temoporfin formulation in a murine tumor model

Research output: Contribution to journalArticle

Abstract

Meso-tetra(hydroxyphenyl)chlorin (mTHPC) (INN: Temoporfin) is one of the most potent photodynamically active substances in clinical use. Treatment protocols for Temoporfin-mediated photodynamic therapy often rely on drug-light intervals of several days in order for the photosensitizer to accumulate within the target tissue, though tumor selectivity is limited. Here, the mTHPC localization was studied at 2-8 h following systemic administration of a liposomal Temoporfin formulation (0.15 mg kg(-1) b.w.) in HT29 human colon adermcarcinoma in NMRI nu/nu mice. Photosensitizer distribution within tumor and internal organs was investigated by means of high performance liquid chromatography following chemical extraction, as well as in situ fluorescence imaging and point-monitoring fluorescence spectroscopy. For tumor tissue, the Temoporfin concentrations at 4 h (0.16 +/- 0.024 ng mg(-1)) and 8 h (0.18 +/- 0.064 ng mg(-1)) were significantly higher than at 2 It (0.08 +/- 0.026 ng mg(-1)). The average tumor-to-muscle and the tumor-to-skin selectivity were 6.6 and 2, respectively, and did not vary significantly with time after photosensitizer injection. In plasma, the Temoporfin concentration was low (0.07 +/- 0.07 ng mg(-1)) and showed no significant variation with time. Our results indicate a rapid biodistribution and clearance from the bloodstream. Within the same type of organ, data from both fluorescence methods generally exhibited a significant correlation with the extraction results.

Details

Authors
  • Jenny Svensson
  • Ann Johansson
  • S Grafe
  • B Gitter
  • T Trebst
  • N Bendsoe
  • Stefan Andersson-Engels
  • Katarina Svanberg
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Atom and Molecular Physics and Optics
Original languageEnglish
Pages (from-to)1211-1219
JournalPhotochemistry and Photobiology
Volume83
Issue number5
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes