Invited Symposium: Photodynamic Therapy
Busch, T (PDT Center, Roswell Park Cancer Institute, Buffalo, USA)
Oseroff, AR (Department of Dermatology, Roswell Park Cancer Institute, Buffalo, USA)
It is well established that in PDT of solid tumors fluence rate can significantly influence treatment outcome. This can be attributed to the fluence rate dependence of tissue oxygenation (1, 2, 3). High tissue oxygen consumption during delivery of light at high fluence rate has been demonstrated, with a resulting oxygen deficit for singlet oxygen generation and therefore less efficient treatment. Conversely, maintenance of tumor oxygenation during PDT with light at low fluence rate can also be demonstrated , with a resulting increase in treatment efficiency. Increased PDT efficiency is, at least in part, due to enhanced direct tumor cell photodamage, as well as to effects of fluence rate on the vascular response, especially that of the tumor surrounding normal vasculature. Preclinically, PhotofrinÒ PDT at high fluence rate (150 mW/cm2) can almost completely protect the normal skin vasculature, while low fluence rate treatment (30 mW/cm2) can lead to total vascular collapse within 1 hour. Collapse of the tumor vasculature occurs regardless of fluence rate. Administration of the nitric oxide synthase inhibitor L-NNA can abrogate the protection of the normal vasculature by high fluence rate treatment and enhance long term tumor control, but has no effect with low fluence rate PDT. Tumor pO2 histograms of clinical measurements in basal cell carcinoma lesions during Photofrin® (1 mg/kg) PDT show a marked shift towards hypoxia with an incident light fluence rate of 150 mW/cm2 and an apparent shift towards increased oxygenation with an incident fluence rate of 30 mW/cm2. It is too early to determine whether this increased oxygenation during treatment will translate into therapeutic gain.
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|Henderson, B; Busch, T; Oseroff, AR; (1998). Effects of Fluence Rate on Tumor Oxygenation and Vascular Responses to Photodynamic Therapy (PDT).. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/rainbow/henderson0767/index.html|
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