<title>Effect of thrombocytopenia on the efficacy of Photofrin-based photodynamic therapy in vivo</title>

Abstract

Neutrophils are indispensable for successful PDT. Recently it has been observed that the administration of anti-thrombocyte antiserum prevents the occlusion of the microvasculature that normally occurs upon Photofrin-based PDT. We hypothesized that this antiserium treatment would increase the therapeutic efficacy by facilitating the accumulation of neutrophils at the lesion. To study this we implanted the isologous rhabdomyosarcoma R-1 subcutaneously into the thigh of WAG/Raj rats, and treated the tumor by interstitial Photofrin-based PDT. We found that the increasing tumor doubling time after PDT under anti-thrombocyte antiserum-induced thrombocytopenia was significantly higher that in normal rats. Strikingly, the increase in tumor doubling time did not differ if thrombocytopenia was induced before or immediately after illumination. At least 1.5 times more neutrophils than normal accumulated into the PDT-treated tumors under thrombocytopenia. If the rats were rendered granulocytopenic by the administration of anti-granulocyte antiserum first followed by anti-thrombocyte antiserum post PDT, this lead to a considerable loss of the thrombocytopenia- dependent gain in the efficacy of PDT. These findings suggest that the increased accumulation of neutrophils into the tumor underlie the enhanced efficacy of PDT and may implicate that under normal clinical conditions the full granulocyte-dependent kill potential is not utilized due to the presence of activated thrombocytes that cause blood flow stasis.