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

Svensson, Jenny LU ; Johansson, Ann LU ; Grafe, S; Gitter, B; Trebst, T; Bendsoe, N; Andersson-Engels, Stefan LU and Svanberg, Katarina LU (2007) In Photochemistry and Photobiology 83(5). p.1211-1219
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... (More)
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. (Less)
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organization
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type
Contribution to journal
publication status
published
subject
in
Photochemistry and Photobiology
volume
83
issue
5
pages
1211 - 1219
publisher
American Society for Photobiology
external identifiers
  • wos:000249881400027
  • scopus:34548733709
ISSN
0031-8655
DOI
10.1111/j.1751-1097.2007.00146.x.
language
English
LU publication?
yes
id
765cb90d-1629-466a-91d3-36d6799eb4fa (old id 2259586)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17880517&dopt=Abstract
date added to LUP
2012-02-07 09:52:26
date last changed
2017-07-23 04:52:39
@article{765cb90d-1629-466a-91d3-36d6799eb4fa,
  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.},
  author       = {Svensson, Jenny and Johansson, Ann and Grafe, S and Gitter, B and Trebst, T and Bendsoe, N and Andersson-Engels, Stefan and Svanberg, Katarina},
  issn         = {0031-8655},
  language     = {eng},
  number       = {5},
  pages        = {1211--1219},
  publisher    = {American Society for Photobiology},
  series       = {Photochemistry and Photobiology},
  title        = {Tumor selectivity at short times following systemic administration of a liposomal temoporfin formulation in a murine tumor model},
  url          = {http://dx.doi.org/10.1111/j.1751-1097.2007.00146.x.},
  volume       = {83},
  year         = {2007},
}