contrast and excellent resolution provided by MR with high sensitivity and quantification of radiotracer metabolism provided by PET. Also, unlike the conventional
PET/CT where imaging information is acquired in sequence, PET/MRI allows
simultaneous image acquisition [32], leading to largely improved diagnostic outcomes. Moreover, PET/MRI systems have been successfully conceived for
small-animal imaging [33, 34], accelerating the research for novel bimodal magnetic radiotracers [32, 35]. In this context, radiolabeled magnetic NPs have gained
much attention lately as dual-modality imaging agents due to their ability to act not
only as imaging tracers for PET or SPECT but also as MRI contrast agent [33].
Approaches involving chelator-free and chelator-based radiolabeling have been
reported in an array of differently designed and surface-functionalized IONPs with
different radioisotopes, suited for both SPECT and PET.
To date, IONPs have been radiolabeled with various types of suitable radionuclides for SPECT imaging. Technetium-99 m (
99m
Tc), the most commonly used
radioisotope in SPECT in its reduced form (
99m
TcO 2 ), can react with electron donor
groups and can, be linked to IONPs through the –COO
− group of chelating agents
DTPA and NOTA or –NH 2 group of chitosan and modified PEG [36]. Madru et al.
[36] developed
99m
Tc-labeled IONPs (radiolabeling yield * 99%) for SPECT/MRI
imaging of sentinel lymph nodes, by conjugating the reduced state of
99m TcO
4− to
the functionalized PEG coating on the IONP surface. An impressive uptake value of
200%ID/g (percentage of injected dose per gram of tissue) was found for
99m Tc-IONPs SLN tissue, whereas less than 2%ID/g was found in the liver and
spleen. IONPs have also been labeled with multiple other radioisotopes for SPECT,
such as
125 I [37],
131 I [38, 39],
111 In [40, 41] and
188 Re [42] and further review can
be found elsewhere [43].
The increasing availability of PET imaging isotopes together with the optimization of the radiolabeling methods, as well as its greater sensitivity when
compared to SPECT, have contributed to the greater success of PET imaging in
clinical and preclinical settings. In this context, several PET radioisotopes have
been used to radiolabel iron oxide NPs, such as
64 Cu [44–46],
68 Ga [47],
18 F [48],
11 C [33],
89 Zr [49],
69 Ge [50]. For example,
64 Cu-labeled SPIONS conjugated with
DOX and functionalized with cRGD were developed for targeted theranostic purposes [45]. The targeted NPs had significantly higher tumor accumulation when
compared to non-targeted SPIONs. The MRI r 2 relaxivity of the SPIO nanocarriers
was measured to be similar to that of the Ferridex
® ; an FDA approved SPIO-based
MRI contrast agent. De Rosales et al. [46] directly radiolabeled SPIONs with a
dithiocarbamate bisphosphonate (DTCBP) that binds to both
64 Cu and the NP,
leaving the nanosystem polymeric coating (dextran) unaffected. Using the lymphatic system as in vivo model, the popliteal lymph nodes of a C57BL/6 mouse
were located using T2*-weighted MR images (Fig. 2.1a). PET imaging confirmed
the uptake of NPs in both popliteal and iliac lymph nodes (Fig. 2.1b, c). Hence,
[
64 Cu(DTCBP) 2 ]–Endorem was a successful PET–MR dual-modality imaging
agent that accumulated in draining lymph nodes.
Following the emerging concept of intrinsically radiolabeled NPs, in a study
by Boros et al. [49] IONPS were successfully chelator-free radiolabeled with
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
17
PET/CT where imaging information is acquired in sequence, PET/MRI allows
simultaneous image acquisition [32], leading to largely improved diagnostic outcomes. Moreover, PET/MRI systems have been successfully conceived for
small-animal imaging [33, 34], accelerating the research for novel bimodal magnetic radiotracers [32, 35]. In this context, radiolabeled magnetic NPs have gained
much attention lately as dual-modality imaging agents due to their ability to act not
only as imaging tracers for PET or SPECT but also as MRI contrast agent [33].
Approaches involving chelator-free and chelator-based radiolabeling have been
reported in an array of differently designed and surface-functionalized IONPs with
different radioisotopes, suited for both SPECT and PET.
To date, IONPs have been radiolabeled with various types of suitable radionuclides for SPECT imaging. Technetium-99 m (
99m
Tc), the most commonly used
radioisotope in SPECT in its reduced form (
99m
TcO 2 ), can react with electron donor
groups and can, be linked to IONPs through the –COO
− group of chelating agents
DTPA and NOTA or –NH 2 group of chitosan and modified PEG [36]. Madru et al.
[36] developed
99m
Tc-labeled IONPs (radiolabeling yield * 99%) for SPECT/MRI
imaging of sentinel lymph nodes, by conjugating the reduced state of
99m TcO
4− to
the functionalized PEG coating on the IONP surface. An impressive uptake value of
200%ID/g (percentage of injected dose per gram of tissue) was found for
99m Tc-IONPs SLN tissue, whereas less than 2%ID/g was found in the liver and
spleen. IONPs have also been labeled with multiple other radioisotopes for SPECT,
such as
125 I [37],
131 I [38, 39],
111 In [40, 41] and
188 Re [42] and further review can
be found elsewhere [43].
The increasing availability of PET imaging isotopes together with the optimization of the radiolabeling methods, as well as its greater sensitivity when
compared to SPECT, have contributed to the greater success of PET imaging in
clinical and preclinical settings. In this context, several PET radioisotopes have
been used to radiolabel iron oxide NPs, such as
64 Cu [44–46],
68 Ga [47],
18 F [48],
11 C [33],
89 Zr [49],
69 Ge [50]. For example,
64 Cu-labeled SPIONS conjugated with
DOX and functionalized with cRGD were developed for targeted theranostic purposes [45]. The targeted NPs had significantly higher tumor accumulation when
compared to non-targeted SPIONs. The MRI r 2 relaxivity of the SPIO nanocarriers
was measured to be similar to that of the Ferridex
® ; an FDA approved SPIO-based
MRI contrast agent. De Rosales et al. [46] directly radiolabeled SPIONs with a
dithiocarbamate bisphosphonate (DTCBP) that binds to both
64 Cu and the NP,
leaving the nanosystem polymeric coating (dextran) unaffected. Using the lymphatic system as in vivo model, the popliteal lymph nodes of a C57BL/6 mouse
were located using T2*-weighted MR images (Fig. 2.1a). PET imaging confirmed
the uptake of NPs in both popliteal and iliac lymph nodes (Fig. 2.1b, c). Hence,
[
64 Cu(DTCBP) 2 ]–Endorem was a successful PET–MR dual-modality imaging
agent that accumulated in draining lymph nodes.
Following the emerging concept of intrinsically radiolabeled NPs, in a study
by Boros et al. [49] IONPS were successfully chelator-free radiolabeled with
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
17