EFFECTS OF PHOTODYNAMIC THERAPY USING MONO-L-ASPARTYL CHLORIN E(6) ONVESSEL CONSTRICTION, VESSEL LEAKAGE, AND TUMOR RESPONSE

The effect of photodynamic therapy using mono-L-aspartyl chlorin e(6) (NPe6) on both direct cytotoxicity and vascular damage was examined. S prague-Dawley rats bearing chondrosarcoma tumor were given i.v. inject ions of 5 or 10 mg/kg NPe6 and exposed to 135-J/cm(2) 664-nm laser lig ht either 4 or 24 h after NPe6 injection. The percentage of viable tum or cells was estimated either immediately after the completion of ligh t treatment or 24 h after treatment using a (4,5-dimethylthiazol-2-yl) -2,5-diphenyltetrazolium bromide assay. Measurements of arteriole cons triction and venule leakage in normal cremaster tissues were made duri ng and 1 h after the light treatment. Tumor response was evaluated for the 4 different NPe6 dose and time combinations. Both direct tumor cy totoxicity and vascular stasis were observed during light treatment. V essel leakage did not occur. Blood flow stasis was a result of platele t aggregation and the mechanical obstruction of flow rather than vesse l constriction. The magnitude of direct cytotoxicity and vascular resp onse was dependent on both the amount of NPe6 delivered and the delay between injection and light treatment. Tumor cure was found in animals either when given high NPe6 doses or when treated early after NPe6 in jection. Treatment regimens which maximized the effect of both vascula r stasis and direct tumor cytotoxicity were found to produce the best tumor response. Dose combinations which produced vascular stasis with minimal early cytotoxicity did not result in cure. The combined mechan isms of damage after photodynamic therapy using NPe6 suggests that thi s photosensitizer may have specific advantages for clinical use and pr ovides a benchmark for the development of new photosensitizers.