generality of these observations. Scherz and coworkers found that
phototoxicity of Tookad toward cell cultures is higher than that of
Stakel, although Stakel generates mainly hydroxyl radical, as
opposedtoTookad( 107 ).ThecontrastwiththecaseofH 2 TClPPOH
versus H 2 TClPBOH is probably related to the fact that Tookad is a
hydrophobic sensitizer, whereas Stakel is hydrophilic and their
intracellular localizations must be different.
A superficial appraisal ofTable V suggests that Photofrin is
nearly as good a sensitizer as H 2 TClPBOH for PDT of melanoma.
A more careful examination reveals that the onset of Photofrin
cytotoxicity in the dark occurs at concentrations one order of
magnitude lower than those of halogenated and sulfonated TPPs
chlorins or bacteriochlorins. In an attempt to compare the
in vitro efficacy of different sensitizers, Plaetzer defined the
IC 50 of a sensitizer as the ratio between its lethal dose 50% in
the dark and induced by light, IC 50 ¼LD50dark/LD50PDT ( 104 ).
This is a very convenient index to characterize the effectiveness
of a series of sensitizers under the same light dose. However, to
compare experiments employing different light doses, it is neces-
sary to incorporate the light dose in the evaluation of sensitizers.
We can obtain a figure of merit to characterize thein vitroeffi-
cacy of a sensitizer using the dark cytotoxicity measured by
LD50dark, together with the concentration required to kill 90%
of the cells for a given light dose (hn 90 )
fPDT¼LD50dark
LD90PDThn 90(20)The equation above defines a phototherapeutic index and was
appliedtoinvitrostudiesforwhichalltheparametersareavailable.
Table VI presents a few relevant examples. The comparison
between Photofrin and Foscan is straightforward because the same
celllinewasemployedandrevealsthattheFoscanisamoreefficient
sensitizer. The comparison between the other sensitizers involves
different cell lines and must be made with caution. However, sul-
fophenylbacteriochlorins with chlorine atoms in theortho-positions
of the four phenyl rings have shown similar dark cytotoxicities and
phototoxicities toward various cell lines (89,100,105) and seem to
be promising sensitizers for oncologic PDT.
Sensitizers that are successfulin vitromay failin vivobecause
of poor biodistribution/bioavailability, unfavorable pharmacoki-
netics, or unwanted side effects. As mentioned inSection I, the
choice of porphyrin derivatives for the PDT of cancer is driven,
in part, by their affinity toward tumors. Hence, biodistribution/
bioavailability is not generally a problem with these sensitizers,
224 LUIS G. ARNAUT