2 Aptamer-Based Probes for Molecular Imaging
37
tumor targeting ability of this aptamer, similar to the finding in SPECT imaging
studies. In 2016, Park et al. developed a complementary oligonucleotide (cODN)
hybridization-based aptamer conjugation platform and evaluated the same AS141
aptamer (
18 F-hyAS1411) [35]. The cODN platform has a high hybridization efficiency, which makes it possible to easily radiolabel several aptamers at the same
time. The cODN was prelabeled with
18 F and hybridized with a matched sequence
containing aptamers in aqueous conditions. The tumor uptake was slightly higher
than the control sequence. But both
18 F-hyAS1411 and the control sequence had
same absorption in the kidneys, intestines, and liver most probably due to fast blood
clearance of aptamers.
Aptamer TTA1, an RNA aptamer against the extracellular matrix protein tenascin
C, has also been radiolabeled with positron-emitting radionuclides as the PET
imaging probe. Tavitian et al. reported the
18 F-TTA1, which was evaluated in U251
glioblastoma xenografted mice [36]. A maximum uptake of 1.7% injected dose/cc
was achieved in the tumor at 15 min after injection, but unspecific muscular uptake
was high, yielding a tumor-to-muscle ratio of 2.3 at 15 min and 5.4 at 90 min.
Jacobson et al. evaluated two other aptamers against tenascin-C as probes for PET
imaging [37]. In the study, an aptamer was performed first and radiolabeled with
either
64 Cu or
18 F before being evaluated by PET imaging in subcutaneous xenograft
tumor-bearing mice. Two labeling strategies showed higher uptake by the tumor than
a scrambled control sequence.
2.3 Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is known to be the prominent and powerful
neuroimaging modality, allows 3D imaging of the whole human body with clinically
available instruments all over the world [38]. MRI uses strong magnetic fields, electric
field gradients, and radio waves to generate images with very high spatial resolution,
excellent soft-tissue contrast, and unlimited penetration depth. Nowadays, MRI is an
effective choice in imaging techniques when there are little difference and molecular
information in tissues (like a solid tumor and a regular tissue).
It is preferred to use contrast agents in MRI to detect molecular markers of the
tumor before the tumor gets any worse. MR contrast agents include T1-positive
paramagnetic agents and T2-negative superparamagnetic nanoparticles. These new
smart contrast agents can remarkably promote the imaging sensitivity and diagnostic
accuracy by shortening the T1 (longitudinal) or T2 (transverse) relaxation time of
neighboring water protons [39]. To achieve this goal, several studies were conducted
to specifically address the improvement of MRI by aptamer-based probes.
Because of their greater properties over gadolinium-based contrast agents, a
new class of MRI contrast agents, superparamagnetic iron oxide nanoparticles, are
catching the attention of many researchers. It has been reported that superparamagnetic iron oxide nanoparticles coupled biological molecules including thiol modified
oligonucleotides had active targeting capability. In 2001, Weissleder et al. reported
37
tumor targeting ability of this aptamer, similar to the finding in SPECT imaging
studies. In 2016, Park et al. developed a complementary oligonucleotide (cODN)
hybridization-based aptamer conjugation platform and evaluated the same AS141
aptamer (
18 F-hyAS1411) [35]. The cODN platform has a high hybridization efficiency, which makes it possible to easily radiolabel several aptamers at the same
time. The cODN was prelabeled with
18 F and hybridized with a matched sequence
containing aptamers in aqueous conditions. The tumor uptake was slightly higher
than the control sequence. But both
18 F-hyAS1411 and the control sequence had
same absorption in the kidneys, intestines, and liver most probably due to fast blood
clearance of aptamers.
Aptamer TTA1, an RNA aptamer against the extracellular matrix protein tenascin
C, has also been radiolabeled with positron-emitting radionuclides as the PET
imaging probe. Tavitian et al. reported the
18 F-TTA1, which was evaluated in U251
glioblastoma xenografted mice [36]. A maximum uptake of 1.7% injected dose/cc
was achieved in the tumor at 15 min after injection, but unspecific muscular uptake
was high, yielding a tumor-to-muscle ratio of 2.3 at 15 min and 5.4 at 90 min.
Jacobson et al. evaluated two other aptamers against tenascin-C as probes for PET
imaging [37]. In the study, an aptamer was performed first and radiolabeled with
either
64 Cu or
18 F before being evaluated by PET imaging in subcutaneous xenograft
tumor-bearing mice. Two labeling strategies showed higher uptake by the tumor than
a scrambled control sequence.
2.3 Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is known to be the prominent and powerful
neuroimaging modality, allows 3D imaging of the whole human body with clinically
available instruments all over the world [38]. MRI uses strong magnetic fields, electric
field gradients, and radio waves to generate images with very high spatial resolution,
excellent soft-tissue contrast, and unlimited penetration depth. Nowadays, MRI is an
effective choice in imaging techniques when there are little difference and molecular
information in tissues (like a solid tumor and a regular tissue).
It is preferred to use contrast agents in MRI to detect molecular markers of the
tumor before the tumor gets any worse. MR contrast agents include T1-positive
paramagnetic agents and T2-negative superparamagnetic nanoparticles. These new
smart contrast agents can remarkably promote the imaging sensitivity and diagnostic
accuracy by shortening the T1 (longitudinal) or T2 (transverse) relaxation time of
neighboring water protons [39]. To achieve this goal, several studies were conducted
to specifically address the improvement of MRI by aptamer-based probes.
Because of their greater properties over gadolinium-based contrast agents, a
new class of MRI contrast agents, superparamagnetic iron oxide nanoparticles, are
catching the attention of many researchers. It has been reported that superparamagnetic iron oxide nanoparticles coupled biological molecules including thiol modified
oligonucleotides had active targeting capability. In 2001, Weissleder et al. reported