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Fig. 5 Whole-body fluorescence imaging of (a) control mouse, (b) cyanine dye 8,(c) conjugate
11, and (d) conjugate 12 at a dose of 0.3
μ
mol/kg, 24 h post-intravenous injection
The free base showed significant in vitro PDT efficacy, but limited tumor avidity
in mice bearing tumors, whereas the corresponding Ni(II) derivative did not
produce any PDT-mediated cell kill but showed excellent tumor-imaging ability
at a dose of 0.3
mol/kg at 24, 48, and 72 h postinjection (Figs.
4
and
5
). The limited
PDT efficacy of Ni(II) analog could be due to its inability to produce singlet
oxygen. Based on electrochemical and spectroelectrochemical data in DMSO, the
first one-electron oxidation and the first one-electron reduction of both the free base
and the corresponding Ni(II) conjugates were centered, while the second
one-electron reduction of the two conjugates is assigned to the purpurinimide part
of the molecule. Reduction of the CD unit is facile and occurs prior to reduction of
the purpurinimide group, suggesting that the CD unit could be a driving force to
quench the produced singlet oxygen as an oxidant. An obvious interaction between
the CD and the purpurinimide group is observed for the free-base conjugate, as
compared to a negligible interaction between two the functional groups in the case
of the Ni(II) conjugate. As a result, the larger HOMO-LUMO gap of the free-base
conjugate and the corresponding smaller quenching constant is considered to be a
reason to avoid singlet oxygen quenching to some degree.
μ
2.2 MR/Fluorescence Imaging and PDT
Currently, the most widespread MRI contrast agents (CAs) are gadolinium (Gd)-
based nonspecific agents such as Magnevist
®
(Gd-DTPA) for contrast enhancement
(CE). While providing powerful contrast efficacy and excellent safety in patients
without severe dysfunction, these CAs lack real specificity for depicting certain
tissue, organ, and disease. These characteristics have limited the diagnostic capac-
ity of contrast-enhanced MRI in both clinical and experimental settings.
Therefore, the use of tumor-avid porphyrin-based compounds as vehicles to
deliver the Gd(III) ion to tumor has been investigated in various laboratories.
Since the ring structure of porphyrins and chlorins are too small to adequately
accommodate Gd, Gd-labeled porphyrins and metalloporphyrins were difficult to
synthesize and found to be unstable. However, in expanded porphyrin systems, the
Gd can be inserted with a high stability of the resulting product, and certain Gd
analogs, e.g., Gd(III) Texaphyrin [
59
], are under clinical trials with promising
