Photodynamic therapy (
PDT) is an experimental treatment modality for malignant
tumors. It is based on the principle that a
photosensitizer, such as
hematoporphyrin derivative (HPD), is retained in higher concentrations in
tumors than in surrounding nonmalignant tissues and that photoactivation of the sensitizer can be used to evoke
tumor destruction. However, retention of the systemic injection of HPD is not limited to malignant tissues. This lack of specific
tumor localization thus reduces the therapeutic ratio of the treatment and causes skin photosensitivity and possible systemic toxicity. Injection of HPD directly into the
tumor, on the other hand, has been shown to yield higher levels of the
drug in the
tumor and lower levels in normal tissues, in comparison with systemic administration. In this study, we examined the photodynamic effect on s.c. implanted mouse
bladder tumors subjected to intratumor (i.t.) and i.p. HPD
injections.
Tumor cell killing, measured by cell survival, was observed in both the it. and i.p. groups and was dependent on fluence and HPD dosage. However, no significant enhancement of cell killing was observed in the i.t. injected
tumors, despite the higher
porphyrin levels in these
tumors. Histological examination of the effect of
PDT on the blood vessels indicated that while cell death accompanied severe
hemorrhage in the i.p. injected
tumors, in the i.t.
tumors there was much less
hemorrhage and intact blood vessels remained. This observation suggests that with i.t. administration, direct photodynamic action may play a significant role in the
tumor cell killing, in contrast to systemic administration, in which destruction of the blood vessels is believed to be the main cause of
tumor destruction.