Photochemistry and Photobiology, 2003, 78(6) 613
by PDT would increase, especially in the case of spheroids (40).
On the other hand, a subcellular relocalization of the photosensi-
tizer during a 30 min light exposure could also take place, as seen
for other photosensitizers (41), affecting the overall cell killing.
However, only under conditions where the highest concentration
of the photosensitizer in combination with a 24 h incubation was
used could a small improvement in the photocytotoxic effect be
observed. However, and more likely, it is presumed that especially
the low concentrations of the photosensitizers typically found in
the deeper layers of the spheroids fully explain the resistance of the
cellular aggregates against PDT observed with the hypericins.
In summary, our results show that the iodinated analogs of
hypericin do not possess a higher cytotoxic effect than hypericin
upon irradiation in either monolayers or spheroids. Furthermore,
our study demonstrates that although in a preclinical phase it is
tempting to use monolayers as a simple way to evaluate the in vivo
potential of newly developed photosensitizers, the use of 3-D cell
aggregates resembling the in vivo situation much better is critical
for a correct evaluation of their efficacy.
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Acknowledgements—We thank Paula Aertsen and Lydie Vanrykel (De-
partment of Pathology) for excellent technical assistance. This work was
supported by grants awarded by Fonds voor Wetenschappelijk Onder-
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