To this end, AuNPs have been radiolabeled with a number of isotopes for use with
SPECT or PET, and more in-depth information regarding the application of radiolabeled AuNPs can be found in recently published review papers [1, 16, 64, 65].
Macrocyclic chelating ligands are usually used for the labeling of AuNPs with a
SPECT or PET radionuclide [1]. Ocampo-Garcia et al. [66] evaluated the potential
of
99m Tc-labelled gold NPs (*20 nm) with good radiolabeling yield (>95%) and
good stability in human serum, conjugated to the HYNIC-Gly-Gly-Cys-NH 2
(HYNIC-GGC) peptide and thiol-mannose, as agent for sentinel lymph node
(SLN) identification. Biodistribution studies and in vivo SPECT/CT images of
Wistar rats demonstrated a clear lymph node uptake (11.58 ± 1.98%ID at 1 h) that
remained constant for 24 h with low accumulation in the kidneys (0.98 ± 0.10%
ID) and insignificant uptake in all other organs. AuNPs have also been labeled with
PET isotopes through chelator-based methods [67]. For example, Xie et al. [68],
reported gold nanoshells coated with PEG 2k -DOTA radiolabeled with
64 Cu for
tumor diagnosis. The radiolabeling efficiency was 81.3%, and PET imaging
demonstrated that AuNPs showed higher accumulation at the tumor site, mainly at
20 and 44 h p.i. [68]. In an interesting study performed by Chen et al. [69], the
kinetics of renal clearable Au NPs were analyzed by dynamic PET imaging of
ultrasmall (*3 nm)
64 Cu–NOTA–Au–GSH. It is possible to observe, in the PET/
CT image (Fig. 2.3a), a predominant uptake of NPs in the bladder (yellow arrow)
and kidneys (red arrows). The NPs demonstrated rapid renal clearance (%75%ID,
24 h p.i.) and drastically reduced hepatic uptake. The elimination half-life of *6
min was found to be over 130-times shorter than previously reported for similar
NPs [70], thereby indicating the superiority of PET in accurately assessing the
in vivo pharmacokinetics of intravenously injected NPs [69]. In another study [71],
AuNPs conjugated with Cetuximab (a specific antibody against EGFR) were
radiolabeled with
89 Zr using desferrol as a chelator agent. The nanoprobe predominantly accumulated in the liver (red arrows) and in the A431 tumors implanted
in both legs (green arrows), as shown in Fig. 2.3b. Maximum tumor uptake was
observed at 48 h p.i., with a 12.0 ± 2.3 tumor-to-background ratio. The radiolabeled NPs proved to be a successful PET imaging agent and a potentially therapeutic alternative approach [71].
Nuclear bombardment, radiochemical synthesis, and post-synthetic radiolabeling
are some chelator-free approaches that have been proposed for AuNPs radiolabeling
[72]. Using the hot-plus-cold method, trace levels of radioactive (hot) precursor
64 CuCl 2 were mixed with non-radioactive (cold) gold chloride copper acetylacetonate precursors during the synthesis [73] to yield
64 Cu-alloyed AuNP
(
64 CuAuNPs). This strategy resulted in a good radiolabeling stability, without any
degradation or transchelation in mouse serum up to 48 h, as well as improved
in vivo stability when compared with
64 Cu-DOTA. Mice bearing EMT-6 tumors
were used to assess the passive targeting capability of
64 CuAuNPs and tumor
metabolism was also evaluated in comparison to
18 F-fluorodeoxyglucose
(
18 F-FDG) (Fig. 2.4).
64 CuAuNPs demonstrated similar tumor accumulation
(4.93 ± 0.32%ID/g) as that of
18 F-FDG (4.59 ± 0.43%ID/g). Additionally,
enhanced tumor-to-muscle (T/M) ratios were observed (3.99 ± 0.89, 11.9 ± 2.08
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
21
SPECT or PET, and more in-depth information regarding the application of radiolabeled AuNPs can be found in recently published review papers [1, 16, 64, 65].
Macrocyclic chelating ligands are usually used for the labeling of AuNPs with a
SPECT or PET radionuclide [1]. Ocampo-Garcia et al. [66] evaluated the potential
of
99m Tc-labelled gold NPs (*20 nm) with good radiolabeling yield (>95%) and
good stability in human serum, conjugated to the HYNIC-Gly-Gly-Cys-NH 2
(HYNIC-GGC) peptide and thiol-mannose, as agent for sentinel lymph node
(SLN) identification. Biodistribution studies and in vivo SPECT/CT images of
Wistar rats demonstrated a clear lymph node uptake (11.58 ± 1.98%ID at 1 h) that
remained constant for 24 h with low accumulation in the kidneys (0.98 ± 0.10%
ID) and insignificant uptake in all other organs. AuNPs have also been labeled with
PET isotopes through chelator-based methods [67]. For example, Xie et al. [68],
reported gold nanoshells coated with PEG 2k -DOTA radiolabeled with
64 Cu for
tumor diagnosis. The radiolabeling efficiency was 81.3%, and PET imaging
demonstrated that AuNPs showed higher accumulation at the tumor site, mainly at
20 and 44 h p.i. [68]. In an interesting study performed by Chen et al. [69], the
kinetics of renal clearable Au NPs were analyzed by dynamic PET imaging of
ultrasmall (*3 nm)
64 Cu–NOTA–Au–GSH. It is possible to observe, in the PET/
CT image (Fig. 2.3a), a predominant uptake of NPs in the bladder (yellow arrow)
and kidneys (red arrows). The NPs demonstrated rapid renal clearance (%75%ID,
24 h p.i.) and drastically reduced hepatic uptake. The elimination half-life of *6
min was found to be over 130-times shorter than previously reported for similar
NPs [70], thereby indicating the superiority of PET in accurately assessing the
in vivo pharmacokinetics of intravenously injected NPs [69]. In another study [71],
AuNPs conjugated with Cetuximab (a specific antibody against EGFR) were
radiolabeled with
89 Zr using desferrol as a chelator agent. The nanoprobe predominantly accumulated in the liver (red arrows) and in the A431 tumors implanted
in both legs (green arrows), as shown in Fig. 2.3b. Maximum tumor uptake was
observed at 48 h p.i., with a 12.0 ± 2.3 tumor-to-background ratio. The radiolabeled NPs proved to be a successful PET imaging agent and a potentially therapeutic alternative approach [71].
Nuclear bombardment, radiochemical synthesis, and post-synthetic radiolabeling
are some chelator-free approaches that have been proposed for AuNPs radiolabeling
[72]. Using the hot-plus-cold method, trace levels of radioactive (hot) precursor
64 CuCl 2 were mixed with non-radioactive (cold) gold chloride copper acetylacetonate precursors during the synthesis [73] to yield
64 Cu-alloyed AuNP
(
64 CuAuNPs). This strategy resulted in a good radiolabeling stability, without any
degradation or transchelation in mouse serum up to 48 h, as well as improved
in vivo stability when compared with
64 Cu-DOTA. Mice bearing EMT-6 tumors
were used to assess the passive targeting capability of
64 CuAuNPs and tumor
metabolism was also evaluated in comparison to
18 F-fluorodeoxyglucose
(
18 F-FDG) (Fig. 2.4).
64 CuAuNPs demonstrated similar tumor accumulation
(4.93 ± 0.32%ID/g) as that of
18 F-FDG (4.59 ± 0.43%ID/g). Additionally,
enhanced tumor-to-muscle (T/M) ratios were observed (3.99 ± 0.89, 11.9 ± 2.08
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
21