Photodynamic therapy (
PDT) is a locally administered
therapy currently being investigated in various clinical and preclinical settings.
Tumor-host interaction is an important determinant of
tumor biology and response to treatments. Here we report for the first time the effects of
PDT on an orthotopic, murine mammary
tumor model.
PDT utilizes two individually nontoxic components: (a) the localization in the target site of a photosensitizing
drug; and (b) the activation of the
photosensitizer by light of an appropriate wavelength and energy.
PDT after a single dose of the
photosensitizer MV6401 induced
drug dose-dependent, long-term blood flow shut down and
tumor growth delay in the MCaIV
tumor, grown in the mammary fat pad. The plasma half-life of
MV6401 was approximately 20 min, and the
drug was confined to the vascular compartment shortly after administration. However, it accumulated in the interstitial compartment at 2-6 h after the administration. Two equal
MV6401 doses injected 4 h and 15 min before the light administration allowed the
photosensitizer to localize in both vascular and
tumor cell compartments. The fractionated
drug dose
PDT more effectively induced
tumor growth delay than the same total dose given as a single dose either at 4 h or at 15 min before light administration. The long-term effect of the fractionated
drug PDT on blood flow was also more extensive than single-dose
PDT. Fractionated
photosensitizer dosing
PDT offers a new strategy to optimize
PDT therapy.