WST11, a novel water-soluble bacteriochlorophyll derivative; cellular uptake, pharmacokinetics, biodistribution and vascular-targeted photodynamic activity using melanoma tumors as a model

Photochem Photobiol. 2005 Mar-Apr;81(2):342-51. doi: 10.1562/2004-06-14-RA-199.

Abstract

WST11 is a novel negatively charged water-soluble palladium-bacteriochlorophyll derivative that was developed for vascular-targeted photodynamic therapy (VTP) in our laboratory. The in vitro results suggest that WST11 cellular uptake, clearance and phototoxicity are mediated by serum albumin trafficking. In vivo, WST11 was found to clear rapidly from the circulation (t1/2=1.65 min) after intravenous bolus injection in the mouse, whereas a longer clearance time (t1/2=7.5 min) was noted in rats after 20 min of infusion. The biodistribution of WST11 in mouse tissues indicates hepatic clearance (t1/2=20 min), with minor (kidney, lung and spleen) or no intermediary accumulation in other tissues. As soon as 1 h after injection, WST11 had nearly cleared from the body of the mouse, except for a temporal accumulation in the lungs from which it cleared within 40 min. On the basis of these results, we set the VTP protocol for a short illumination period (5 min), delivered immediately after WST11 injection. On subjecting M2R melanoma xenografts to WST11-VTP, we achieved 100% tumor flattening at all doses and a 70% cure with 9 mg/kg and a light exposure dose of 100 mW/cm2. These results provide direct evidence that WST11 is an effective agent for VTP and provide guidelines for further development of new candidates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacteriochlorophylls / chemistry
  • Bacteriochlorophylls / pharmacokinetics*
  • Bacteriochlorophylls / therapeutic use*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism*
  • Endothelial Cells / radiation effects
  • In Vitro Techniques
  • Light
  • Male
  • Melanoma, Experimental / blood supply
  • Melanoma, Experimental / drug therapy*
  • Melanoma, Experimental / metabolism
  • Mice
  • Mice, Nude
  • Molecular Structure
  • Photochemotherapy*
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Rats
  • Rats, Wistar
  • Serum Albumin, Bovine / pharmacology
  • Solubility
  • Sucrose / pharmacology
  • Time Factors
  • Tissue Distribution
  • Water / chemistry
  • Xenograft Model Antitumor Assays

Substances

  • Bacteriochlorophylls
  • Photosensitizing Agents
  • Water
  • Serum Albumin, Bovine
  • Sucrose
  • padeliporfin