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

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.