Photodynamic pathogen inactivation in red cell concentrates with the silicon phthalocyanine Pc 4

The silicon phthalocyanine Pc 4, a photosensitizer activated with red light, has been studied for pathogen inactivation in red blood cell concentrates (RBCC). Pc 4 targets the envelope of pathogenic viruses such as HIV. To protect RBC during the process two main approaches are used: 1. Inclusion of quenchers of reactive oxygen species produced during treatment. Tocopherol succinate was found to be most effective for this purpose. 2. Formulation of Pc 4, a lipophilic compound, in liposomes that reduce its binding to RBC but not to viruses. As a light source we used a light emitting diode array emitting at 660-680 nm. An efficient mixing device ensures homogenous light exposure during treatment of intact RBCC. Treatment of RBCC with 5 mu M Pc 4 and light results in the inactivation off 5.5 log(10) HIV, greater than or equal to 6.6 log(10) VSV, and greater than or equal to 5 log(10) of PRV and BVDV. Parasites that can be transmitted by blood transfusion (P. falciparum and T. cruzi) are even more sensitive than viruses. Following treatment, RBCC can be stored for 28 days at 4 degrees C with hemolysis below 1%. Baboon RBC circulate with an acceptable 24 hr recovery and half-life. Genetic toxicological studies of Pc 4 with or without light exposure are negative. We conclude that a process using Pc 4 and red light can potentially reduce the risk of transmitting pathogens in RBCC used for transfusion.