This study investigates the non-invasive monitoring of photodynamic therapy (PDT) using 99Technetium hexamethylpropyleneamine oxime (99Tc-HMPAO) scintigraphy in both anaplastic (R3327-AT) and well-differentiated (R3327-H) Dunning prostatic tumors. The tumors were treated with interstitial PDT when their volumes reached 2–3 cm³. Qualitative and quantitative data from pre- and post-PDT scintigraphy revealed a light-dose-dependent and time-dependent shutdown of tumor perfusion. Maximal shutdown occurred about 8 hours post-PDT with a 1,600 J light dose. Light exposure 2 hours after the intravenous administration of the photosensitizer (Photofrin II) produced a greater vascular shutdown than exposure 24 hours later. Regional differences in perfusion within treated and non-treated tumors were measured by tomographic procedures, demonstrating light-dose-dependent volumes of perfusion shutdown. These results suggest that PDT may be a useful modality for monitoring early treatment response and scheduling adjuvant bioirreversible chemotherapy targeted at naturally-occurring and induced hypoxia.This study investigates the non-invasive monitoring of photodynamic therapy (PDT) using 99Technetium hexamethylpropyleneamine oxime (99Tc-HMPAO) scintigraphy in both anaplastic (R3327-AT) and well-differentiated (R3327-H) Dunning prostatic tumors. The tumors were treated with interstitial PDT when their volumes reached 2–3 cm³. Qualitative and quantitative data from pre- and post-PDT scintigraphy revealed a light-dose-dependent and time-dependent shutdown of tumor perfusion. Maximal shutdown occurred about 8 hours post-PDT with a 1,600 J light dose. Light exposure 2 hours after the intravenous administration of the photosensitizer (Photofrin II) produced a greater vascular shutdown than exposure 24 hours later. Regional differences in perfusion within treated and non-treated tumors were measured by tomographic procedures, demonstrating light-dose-dependent volumes of perfusion shutdown. These results suggest that PDT may be a useful modality for monitoring early treatment response and scheduling adjuvant bioirreversible chemotherapy targeted at naturally-occurring and induced hypoxia.