Intrapleural photodynamic therapy (PDT) has been used in combination with lung sparing surgery to treat patients with
malignant pleural mesothelioma. The light, photosensitizers and tissue oxygen are the three most important factors
required by type II PDT to produce singlet oxygen, 1O2, which is the main photocytotoxic agent that damages the tumor
vasculature and stimulates the body’s anti-tumor immune response. Although light fluence rate and photosensitizer
concentrations are routinely monitored during clinical PDT, there is so far a lack of a Food and Drug Administration
(FDA)-approved non-invasive technique that can be employed clinically to monitor tissue oxygen in vivo. In this paper,
we demonstrated that blood flow correlates well with tissue oxygen concentration during PDT and can be used in place
of [3O2] to calculate reacted singlet oxygen concentration [1O2]rx using the macroscopic singlet oxygen model. Diffuse
correlation spectroscopy (DCS) was used to monitor the change in tissue blood flow non-invasively during pleural PDT.
A contact probe with three source and detectors separations, 0.4, 0.7 and 1.0-cm, was sutured to the pleural cavity wall of
the patients after surgical resection of the pleural mesothelioma tumor to monitor the tissue blood flow during
intraoperative PDT treatment. The changes of blood flow during PDT of 2 patients are found to be in good correlation
with the treatment light fluence rate recorded by the isotropic detector placed adjacent to the DCS probe. [1O2]rx
calculated based on light fluence, mean photosensitizer concentration, and relative blood flow was found to be 32%
higher in patient #4 (0.50mM) than that for patient #3 (0.38mM).