Prompt assessment of WST11-VTP outcome using luciferase transfected tumors enables second treatment and increase in overall therapeutic rate

Photochem Photobiol. Sep-Oct 2008;84(5):1231-7. doi: 10.1111/j.1751-1097.2008.00340.x. Epub 2008 Apr 8.

Abstract

This study hypothesized that success rate assessment of vascular targeted photodynamic therapy (VTP) of solid tumors 24 h post-treatment may allow prompt administration of a second treatment in case of failure, increasing the overall success rate. Here, we show that treatment of luciferase transfected CT26-luc mouse colon carcinoma tumors in BALB/c mice by VTP with WST11 (a Pd-bacteriochlorophyll-based photosensitizer) allows fast assessment of treatment success 24 h post-treatment, using bioluminescence imaging (BLI). WST11-VTP was found to abolish luciferin bioluminescence in the treated tumors resulting in two types of responses. One, comprising 75% of the mice, signified successful outcome, presenting neither BLI signal nor tumor regrowth (24 h-90 days post-VTP). The second (the remaining 25% of the mice) signified treatment failure, presenting various levels of BLI signal with subsequent tumor regrowth (24 h-90 days). Consequently, the mice that failed the first treatment were treated again. We show that treatment success rate in both VTP sessions was identical and that the cumulative success rate of the treatment increased from 75% to over 90%. These results therefore, present a fast method of assessing VTP outcome and support the feasibility of successive multiple treatments with these sensitizers in the clinical arena. The presented methodology can also be helpful in future preclinical studies, and expedite the development of VTP drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteriochlorophylls / radiation effects
  • Bacteriochlorophylls / therapeutic use*
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / pathology
  • Disease Models, Animal
  • Female
  • Lasers
  • Luciferases / genetics
  • Luciferases / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Photochemotherapy*
  • Photosensitizing Agents / radiation effects
  • Photosensitizing Agents / therapeutic use*
  • Transfection
  • Treatment Outcome
  • Tumor Cells, Cultured

Substances

  • Bacteriochlorophylls
  • Photosensitizing Agents
  • Luciferases
  • padeliporfin