Chemistry Reference
In-Depth Information
To date, most dual-modality and multimodality imaging agents are based on certain nanoparticles [6, 7], which will be
the focus of Chapter 16. In the current chapter, a comprehensive overview of the dual-modality imaging approaches reported
to date that are not based on nanoparticles will be presented. Because molecular imaging with ultrasound is rare and targeted
ultrasound studies almost exclusively use microbubbles as the contrast agents [8, 9] (see Chapter 14), dual-modality imaging
with ultrasound will not be discussed in this chapter.
Molecular imaging relies on the specific delivery of a contrast agent to achieve imaging contrast of the target of
interest over the background; therefore, the design and synthesis of the imaging agents are critical for successful dual-
modality imaging. These agents are typically composed of several different moieties, which include a targeting ligand
(e.g., small molecule, peptide, protein, antibody) and the imaging tags that can be detected by multiple imaging modal-
ities (e.g., radioisotopes, fluorescent dyes, gd
3+
). although direct conjugation of different imaging tags to conform the
dual-modality probe has been reported, a much more common approach is to use a linker to connect them. In many
cases, the function of the linker is not restricted to simply serve as a bridge between the imaging tags, but also to
improve the targeting efficacy and/or pharmacokinetics of the imaging agent. after a thorough literature survey, the
dual-modality imaging agents are divided into the following categories: PET/optical, SPECT/optical, MRI/optical, and
PET/MRI agents.
15.2
pet/optIcal agents
PET imaging has been widely used in clinical oncology for cancer staging and monitoring the therapeutic response to var-
ious anticancer therapies [10, 11]. The success of PET is attributed to many factors, such as superb tissue penetration, which
allows noninvasive visualisation of deep tissues/structures, excellent quantitation capability, wide availability of
18
F-FDg (a
tracer for imaging glucose metabolism), among others. However, imaging with PET alone is far from ideal since it has
relatively poor spatial resolution (a few mm) and does not provide adequate anatomical information.
although optical imaging has only limited use in the clinical setting, such as imaging tissues close to the surface of the
skin (e.g., breast imaging), tissues accessible by endoscopy (such as within the esophagus and colon), and intraoperative
visualisation (typically image-guided surgery), the combination of PET and optical imaging is highly beneficial [12].
Clinically, dual-modality PET/optical agents may be particularly useful in cancer patient management by employing the
whole-body PET scan to identify the location of tumour(s) and optical imaging to guide tumour resection. From a regulatory
perspective, the need for comprehensive toxicity/dosimetry studies in multiple animal species for only one imaging agent
instead of two separate agents (one for each imaging modality) can significantly reduce the development cost and facilitate
future clinical translation of novel imaging agents, which is the bottleneck for moving state-of-the-art molecular imaging
technology into clinical practice and day-to-day patient management. a tabulated summary of PET/optical agents is provided
in Table 15.1 and discussed in detail below.
15.2.1
small Molecule-Based agents
a compound called PS-2, synthesised through electrophilic aromatic iodination with Na
124
I in the presence of iodogen
beads, has been investigated for both PET/optical imaging and photodynamic therapy (Figure 15.1) [13].
taBle 15.1
a tabulated summary of dual-modality pet/optical agents.
Radioisotope
Fluorophore
Targeting ligand
Target
References
124
I
[13]
Porphyrin
-
-
11
C
Styryl dye
-
RNa
[17]
18
F
BODIPy
-
-
[18]
64
Cu
Cy5.5
Knottin 2.5D peptide
Integrin α
v
β
3
/α
v
β
5
[29]
68
ga
800CW
KKaHWgFTlD peptide
MMP-2/9
[36]
64
Cu
Cypate
Octreotate peptide
Somatostatin receptor
[46]
64
Cu
lS-276
DEVD peptide
Caspase-3
[49]
64
Cu
alexaFluor 750
NuB2 mab
CD20
[52]
64
Cu
800CW
Bevacizumab
VEgF
[54]
64
Cu/
89
Zr
800CW
TRC105 mab
CD105/endoglin
[66, 67]
18
F
C7-Cy
Mannosyl-dextran
Mannose receptor
[70]
