Chemistry Reference
In-Depth Information
124
I
H
3
C
O
CH
3
C
2
H
5
H
3
C
NH
N
N
HN
H
CH
3
H
3
C
H
O
H
3
CO
2
C
FIgure 15.1
a small molecule probe for PET/optical imaging of cancer in living mice.
+
OCH
3
N
NH
11
CH
3
+
N
11
CH
3
OCH
3
H
3
CO
[
11
C] E36
[
11
C] E144
CH
3
O
+
N
11
CH
3
N
CH
3
CH
3
[
11
C] F22
FIgure 15.2
11
C-labelled styryl dyes.
PS-2 is a porphyrin-based photosensitiser that exhibits marked fluorescence at 720 nm upon excitation at 540 nm. The
use of a long-lived PET isotope,
124
I (t
1/2
: 4.2 days), was necessary because maximum tumour accumulation of the agent
occurs at 24 h post-injection in mice.
In vivo
investigation in tumour-bearing mice clearly demonstrated the effectiveness of
the probe for PET/optical imaging, which can be used for guiding photodynamic therapy in the future. although
11
C (t
1/2
:
20.3 min.) has not been used as widely as
18
F (t
1/2
: 109.8 min.), due to its much shorter half-life and limited radiochemistry,
recent efforts have been made to synthesise PET/optical imaging agents using
11
C as the positron emitter. Specifically,
11
C-labelling of styryl dyes constitutes an intriguing field to explore because these molecules can target RNa and have been
widely used for visualising RNa metabolism in living cells [14-16]. The inclusion of PET imaging capability may open the
possibilities of new ways to elucidate RNa-related biological processes such as gene expression. In one report, three
styryldye-based PET probes were successfully synthesised (Figure 15.2), in which the quaternary amino groups allowed for
facile
11
C-labelling using [
11
C]methyltriflate as the methylating agent [17]. good radiochemical yield was achieved, and the
final products could be easily purified with solid phase extraction columns because of the presence of quaternary amino
groups.
Recently, an
18
F-labelled BODIPy dye has been reported where direct radiolabelling of the dye was carried out with
KH
18
F
2
[18].
In vivo
imaging in normal mice showed liver and kidney accumulation, corresponding to nonspecific uptake
and metabolic clearance of the probe. No accumulation of
18
F was found in the bone, suggesting good stability of the B-F
bond
in vivo
. Successful correlation between the images obtained by PET and optical scans was validated
ex vivo
. although
the fluorescence emission of BODIPy (~580 nm) makes it unsuitable for
in vivo
imaging, it may have a potential role in
intraoperative surgical guidance.
