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

Abstract

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. 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. 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. 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. VEC injury after a photosensitization reaction to healthy tissue shortly after TS injection might be low enough for the blood vessels to be patent.