There exists little doubt that profound changes occur to both tumor and normal tissue
microvasculature during photodynamic therapy, and that these changes are important in the
process of tumor destruction. We hypothesize that singlet oxygen, produced during light
activation of photosensitizer, interacts with cellular membranes and induces the release of
arachidonic acid metabolites, notably thromboxane, into the intravascular environment. This
leads to vasoconstriction, platelet aggregation, and hemostasis. To test this hypothesis, we
have measured the release of thromboxane into serum as a function of porphyrin and light
doses used in phototherapy. Sprague Dawley rats bearing chondrosarcoma in the right hind
limb were injected with 0-25 mg/kg Photofrin IP'. A catheter was implanted in the carotid
artery 24 h later, and the hind limb exposed to 0-135 J/cm2 630 nm light. Immediately after
treatment, serum was collected and thromboxane levels were measured by radioimmunoassay.
We found significant increases in systemic thromboxane concentrations following
phototherapy at the highest porphyrin and light doses, compared to drug and light controls.
The administration of indomethacin (10 mg/kg i.p.) prior to treatment suppressed the release
of thromboxane from tumor and normal tissues and inhibited hemostasis and tumor response
to phototherapy. These studies have reinforced the important role of arachidonic acid
metabolites in producing vascular damage during phototherapy.