Analysis of the heterogeneity of pO(2) dynamics during photodynamic therapy with verteporfin

Photodynamic therapy (PDT) with verteporfin provides a reliable way to dest roy malignant tissues. Changes in the blood flow and oxygen partial pressur e (pO(2)) during verteporfin-PDT were studied here in the tumor tissue of t he rat mammary R3230Ac carcinoma model. Oxygen microelectrodes (6-12 mum ti p diameter) were used to measure the transients locally within tumors durin g intravenous injection of 1.0 mg/kg verteporfin followed by irradiation 15 min later with 690 nm light at 200 mW/ cm(2), for a cumulative dose of 144 J/cm(2). The observed changes in pO(2) were heterogeneous and there was a difference in the response of low-pO(2) regions relative to higher-pO(2) re gions. The change in pO(2) in hypoxic tissue regions (pO(2) < 8 mmHg) had a cute pO(2) loss after treatment, whereas the response in regions of higher pO(2) (>8 mm Hg) was more heterogeneous with some areas maintaining their p O(2) value after treatment was completed. Blood flow measurements taken on a subset of the animals indicated a significant loss in flow during the ini tial light delivery that remained low after treatment, indicating some vasc ular stasis. The results suggest that hypoxic or poorly perfused vessels ma y be more susceptible to acute stasis than normoxic vessels in this treatme nt protocol.