Phototoxicity of Vascular Endothelial Cells Caused by Contact with Talaporfin Sodium for 15-120 Min: In Vitro and in Vivo Studies

Risa Hamada, Emiyu Ogawa, Tsunenori Arai

Research output: Contribution to journalArticle

Abstract

Objective: To reveal the mechanism of vascular patency in the myocardium after photosensitization immediately after talaporfin sodium (TS) injection in a canine model, we investigated acute injury to vascular endothelial cells (VECs) in vitro and in vivo. Background data: There are many reports of vascular shutdown within the target region in photodynamic therapy with TS. Vascular patency within healthy canine myocardium in which a photosensitization reaction starts immediately after injection of TS has been reported. Materials and methods: TS fluorescence in human umbilical vein endothelial cells and cell lethality were measured with drug contact time (DCT) up to 120 min at 20 μg/mL. Dependence of radiant exposure on cell lethality with 60 min DCT was investigated using two albumin concentrations that corresponded to those in plasma and interstices. Irradiation (21 mW/cm) outside the adventitia of canine cervical veins for 167 or 667 sec was emitted through a diffuser probe 30 min after intravenous injection of TS (2.5 mg/kg). Veins were extracted ∼30 min after the reaction and stained with von Willebrand factor. Results: Intracellular fluorescence increased, but not cell lethality, with increasing DCT. Cell lethality increased gradually and reached 100% over 20 J/cm2 in the albumin concentration in the interstices. Normal VECs were found at the acute phase over 20 J/cm2 with a TS concentration in plasma of ∼14 μg/mL in vivo. Conclusions: VEC injury after a photosensitization reaction to healthy tissue shortly after TS injection might be low enough for the blood vessels to be patent.

Original languageEnglish
Pages (from-to)305-310
Number of pages6
JournalPhotomedicine and Laser Surgery
Volume35
Issue number6
DOIs
Publication statusPublished - 2017 Jun 1

Keywords

  • albumin
  • drug contact time
  • photosensitization reaction
  • Vascular endothelial cell

ASJC Scopus subject areas

  • Biomedical Engineering
  • Radiology Nuclear Medicine and imaging

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