36
D. Li et al.
agent for imaging [27]. Based on the biodistribution in normal mice and DU-145
tumor-bearing mice, higher accumulation of radioactivity in tumor and rapid blood
clearance were seen1 h after injection and it appeared that the excretion route was
via the urinary system. However, the aptamers evaluated in these studies were lack of
negative oligonucleotide control, it is unclear whether tumor uptake was associated
with their selective targeting or higher vascularization of the tumor microenvironment. Indeed, different labeling method can strongly influence the biodistribution of
aptamers. Two chemically modified aptamers that bind to matrix metalloprotease-9
(MMP9), aptamer containing 2
-fluoro [28] and F3B [29], were radiolabeled with
99m Tc-MAG and
111 In–DOTA respectively. Both modified aptamers demonstrated
significantly higher tumor uptake than the control oligonucleotide. But the clearance of 99mTc-MAG-labeled aptamer was the high hepatobilary excretion, the
111 In
-DOTA-labeled aptamer was by the urinary pathway.
In addition to SPECT imaging probes, detection of bacterial infections was another
application of aptamers. Correa et al. pooled and radiolabeled three aptamers against
various structural cell-wall components of bacteria, SA20, SA23, and SA24, with
99m Tc by a direct radiolabeling method [30–32]. Radiolabeling with
99m Tc was efficient, the average radiolabeling yield was 91%. The radiolabeled aptamers were
stable at least 24 h in 0.9% saline solution, Swiss mice plasma and in excess
of cysteine. Assessment of biodistribution of the
99m Tc radiolabeled aptamer at
4 h after administration in the right thigh muscle of Swiss mice infected with S.
aureus suggested that the infected thigh versus the uninfected thigh has a statistically
significant difference in % injected dose/g (target to nontarget ratio of 4.0). These
results demonstrated the bacterial infection could be located by
99m Tc–radiolabeled
aptamers.
2.2.2 Positron Emission Tomography (PET)
Aptamers as probes for PET imaging in several cancer models have been reported.
Most of the aptamers were selected against proteins that are overexpressed at the
surface of cancer cells, closely resembled the aptamer-based SPECT imaging probes.
In 2010, Hwang et al. constructed a multimodal nanoparticle for tracking cancer
cells [33]. Aptamer AS1411 shown binding to surface nucleolin and SCN-NOTA
were loaded on nanoparticles radiolabeled with approximately 40%
67 Ga-citrate
labeling efficiency. The
67 Ga-NOTA-AS1411 nanoparticle exhibited good serum
stability and targeting cancer cell specificity in C6 glioma tumor-bearing nude
mice, whereas the high accumulation in liver was observed by the large size of the
nanoparticle. In 2014, Li et al. evaluated the AS1411 aptamer conjugated with four
different chelators (DOTA, CB-TE2A, DOTA-Bn, and NOTA-Bn), allowing radiolabeling with
64 Cu [34]. The result demonstrated that CB-TE2A was a preferred
chelator with faster in vivo pharmacokinetics, lower liver uptake and higher tumor-tobackground ratio. Aptamer imaging with
64 Cu-CB-TE2A-AS1411 might be feasible
to detect lung cancer, and the selection of chelator changed the biodistribution and
D. Li et al.
agent for imaging [27]. Based on the biodistribution in normal mice and DU-145
tumor-bearing mice, higher accumulation of radioactivity in tumor and rapid blood
clearance were seen1 h after injection and it appeared that the excretion route was
via the urinary system. However, the aptamers evaluated in these studies were lack of
negative oligonucleotide control, it is unclear whether tumor uptake was associated
with their selective targeting or higher vascularization of the tumor microenvironment. Indeed, different labeling method can strongly influence the biodistribution of
aptamers. Two chemically modified aptamers that bind to matrix metalloprotease-9
(MMP9), aptamer containing 2
-fluoro [28] and F3B [29], were radiolabeled with
99m Tc-MAG and
111 In–DOTA respectively. Both modified aptamers demonstrated
significantly higher tumor uptake than the control oligonucleotide. But the clearance of 99mTc-MAG-labeled aptamer was the high hepatobilary excretion, the
111 In
-DOTA-labeled aptamer was by the urinary pathway.
In addition to SPECT imaging probes, detection of bacterial infections was another
application of aptamers. Correa et al. pooled and radiolabeled three aptamers against
various structural cell-wall components of bacteria, SA20, SA23, and SA24, with
99m Tc by a direct radiolabeling method [30–32]. Radiolabeling with
99m Tc was efficient, the average radiolabeling yield was 91%. The radiolabeled aptamers were
stable at least 24 h in 0.9% saline solution, Swiss mice plasma and in excess
of cysteine. Assessment of biodistribution of the
99m Tc radiolabeled aptamer at
4 h after administration in the right thigh muscle of Swiss mice infected with S.
aureus suggested that the infected thigh versus the uninfected thigh has a statistically
significant difference in % injected dose/g (target to nontarget ratio of 4.0). These
results demonstrated the bacterial infection could be located by
99m Tc–radiolabeled
aptamers.
2.2.2 Positron Emission Tomography (PET)
Aptamers as probes for PET imaging in several cancer models have been reported.
Most of the aptamers were selected against proteins that are overexpressed at the
surface of cancer cells, closely resembled the aptamer-based SPECT imaging probes.
In 2010, Hwang et al. constructed a multimodal nanoparticle for tracking cancer
cells [33]. Aptamer AS1411 shown binding to surface nucleolin and SCN-NOTA
were loaded on nanoparticles radiolabeled with approximately 40%
67 Ga-citrate
labeling efficiency. The
67 Ga-NOTA-AS1411 nanoparticle exhibited good serum
stability and targeting cancer cell specificity in C6 glioma tumor-bearing nude
mice, whereas the high accumulation in liver was observed by the large size of the
nanoparticle. In 2014, Li et al. evaluated the AS1411 aptamer conjugated with four
different chelators (DOTA, CB-TE2A, DOTA-Bn, and NOTA-Bn), allowing radiolabeling with
64 Cu [34]. The result demonstrated that CB-TE2A was a preferred
chelator with faster in vivo pharmacokinetics, lower liver uptake and higher tumor-tobackground ratio. Aptamer imaging with
64 Cu-CB-TE2A-AS1411 might be feasible
to detect lung cancer, and the selection of chelator changed the biodistribution and