2 Aptamer-Based Probes for Molecular Imaging
45
2.6 Multimodal Imaging
Each imaging modality has its own advantages or disadvantages. With the development of nanotechnology, multimodal imaging has become the trend in molecular
imaging [33, 76, 77]. There are growing number of hybrid instruments designed to
combine several imaging modalities. Thus, multifunctional imaging probes based on
nanoparticles are being studied to enhance the contrast. Multimodal imaging probes
could fuse the information of different modalities and make up for the shortcomings
of each modality to construct the comprehensive and precise imaging of diseased
tissues or organs [78]. On the one hand, the multifunctional imaging probe itself has
unique physical effects to assist the treatment, such as the thermal effect, cavitation
effect, and acoustic air effect of microbubbles applied in ultrasound imaging. On the
other hand, these imaging probes can be modified or loaded with drugs as multifunctional contrast agents, deliver drugs to the targeting area and enhance the therapeutic
effect [79]. Several such probes have exploited aptamers as specific targeting agents.
Hwang et al. constructed a cobalt–ferrite nanoparticle, which is surrounded by
rhodamine within a silica shell matrix synthesized with the AS1411 aptamer and
radiolabeled with
67 Ga
33 . First, the cellular distribution of the nucleolin protein
was detected by fluorescence confocal microscopy with this multimodal imaging
probe. Then, they used a 1.5-t MRI scanner to obtain phantom MR image as the
probe concentration increased. Further,
67 Ga radionuclide imaging and MRI were
performed with a gamma camera and 1.5-T MR imager, respectively, to obtain
the biodistribution of this probe in subcutaneous tumor-bearing xenograft mice.
Compared with the negative control, higher signal of the
67 Ga radionuclide was
detected in both thighs of the mice with the multimodal-imaging probe at 24 h after
intravenous injection. Only the AS1411 modified aptamer showed dark T2 signals
inside the tumor region in T2-weighted MR images. As a versatile imaging tool for
specific cancer diagnosis, it takes advantage of both properties of SPECT imaging
and MRI, and offers more sensitive, better quantificational and higher resolution
images.
Recently, molecular imaging probes for fluorescence-guided surgery have made
great progresses in identifying tumor margin and executing the tissue resection [80–
82]. There are many imaging modalities available during the surgery, like PET,
SPECT, X-ray CT or MRI [83]. This type of probe can recognize the location
of a tumor during the clinical examination and tumor resection surgery. Li et al.
synthesized the fluorescent gold nanoparticles conjugated with the nucleolin-targeted
AS1411 aptamer and diatrizoic acid as a X-ray CT and fluorescence molecular
contrast agent (Fig. 2.6) [84]. This dual-modal imaging probe was applied to reveal
the tumor location by CT imaging after intravenous injection 30 min in xenograft
mice bearing CL1-5 subcutaneous tumor (Fig. 2.6c). Because the nanoparticles
with the aptamer emitted an orange-red fluorescent signal under ultraviolet light
during surgery (Fig. 2.6d), it was easy to distinguish the tumor from normal tissue
in comparison to the same nanoparticle without an aptamer.
45
2.6 Multimodal Imaging
Each imaging modality has its own advantages or disadvantages. With the development of nanotechnology, multimodal imaging has become the trend in molecular
imaging [33, 76, 77]. There are growing number of hybrid instruments designed to
combine several imaging modalities. Thus, multifunctional imaging probes based on
nanoparticles are being studied to enhance the contrast. Multimodal imaging probes
could fuse the information of different modalities and make up for the shortcomings
of each modality to construct the comprehensive and precise imaging of diseased
tissues or organs [78]. On the one hand, the multifunctional imaging probe itself has
unique physical effects to assist the treatment, such as the thermal effect, cavitation
effect, and acoustic air effect of microbubbles applied in ultrasound imaging. On the
other hand, these imaging probes can be modified or loaded with drugs as multifunctional contrast agents, deliver drugs to the targeting area and enhance the therapeutic
effect [79]. Several such probes have exploited aptamers as specific targeting agents.
Hwang et al. constructed a cobalt–ferrite nanoparticle, which is surrounded by
rhodamine within a silica shell matrix synthesized with the AS1411 aptamer and
radiolabeled with
67 Ga
33 . First, the cellular distribution of the nucleolin protein
was detected by fluorescence confocal microscopy with this multimodal imaging
probe. Then, they used a 1.5-t MRI scanner to obtain phantom MR image as the
probe concentration increased. Further,
67 Ga radionuclide imaging and MRI were
performed with a gamma camera and 1.5-T MR imager, respectively, to obtain
the biodistribution of this probe in subcutaneous tumor-bearing xenograft mice.
Compared with the negative control, higher signal of the
67 Ga radionuclide was
detected in both thighs of the mice with the multimodal-imaging probe at 24 h after
intravenous injection. Only the AS1411 modified aptamer showed dark T2 signals
inside the tumor region in T2-weighted MR images. As a versatile imaging tool for
specific cancer diagnosis, it takes advantage of both properties of SPECT imaging
and MRI, and offers more sensitive, better quantificational and higher resolution
images.
Recently, molecular imaging probes for fluorescence-guided surgery have made
great progresses in identifying tumor margin and executing the tissue resection [80–
82]. There are many imaging modalities available during the surgery, like PET,
SPECT, X-ray CT or MRI [83]. This type of probe can recognize the location
of a tumor during the clinical examination and tumor resection surgery. Li et al.
synthesized the fluorescent gold nanoparticles conjugated with the nucleolin-targeted
AS1411 aptamer and diatrizoic acid as a X-ray CT and fluorescence molecular
contrast agent (Fig. 2.6) [84]. This dual-modal imaging probe was applied to reveal
the tumor location by CT imaging after intravenous injection 30 min in xenograft
mice bearing CL1-5 subcutaneous tumor (Fig. 2.6c). Because the nanoparticles
with the aptamer emitted an orange-red fluorescent signal under ultraviolet light
during surgery (Fig. 2.6d), it was easy to distinguish the tumor from normal tissue
in comparison to the same nanoparticle without an aptamer.