Photodynamic therapy (
PDT) is a light-based
cancer treatment modality. Here we employed both in vivo and ex vivo fluorescence imaging to visualize vascular response and
tumor cell survival after
verteporfin-mediated
PDT designed to target
tumor vasculature. EGFP-MatLyLu prostate
tumor cells, transduced with EGFP using lentivirus vectors, were implanted in athymic nude mice. Immediately after
PDT with different doses of
verteporfin,
tumor-bearing animals were injected with a
fluorochrome-labeled
albumin. The extravasation of fluorescent
albumin along with
tumor EGFP fluorescence was monitored noninvasively with a whole-body fluorescence imaging system. Ex vivo fluorescence microscopy was performed on frozen sections of
tumor tissues taken at different times
after treatment. Both in vivo and ex vivo imaging demonstrated that vascular-targeting
PDT with
verteporfin significantly increased the extravasation of
fluorochrome-labeled
albumin in the
tumor tissue, especially in the
tumor periphery. Although
PDT induced substantial vascular shutdown in interior blood vessels, some peripheral
tumor vessels were able to maintain perfusion function up to 24 hr
after treatment. As a result, viable
tumor cells were typically detected in the
tumor periphery in spite of extensive
tumor cell death. Our results demonstrate that vascular-targeting
PDT with
verteporfin causes a dose- and time-dependent increase in vascular permeability and decrease in blood perfusion. However, compared to the interior blood vessels, peripheral
tumor blood vessels were found less sensitive to
PDT-induced vascular shutdown, which was associated with subsequent
tumor recurrence in the
tumor periphery.