125 I-sulfo-SHPP and biodistribution results from gamma counting and SPECT/CT
imaging were in agreement with previously published papers [101].
Following a research trend, several studies have been reported indicating that
QDs can provide a multifunctional nanoplatform for multimodality imaging and
therapy that is especially suitable for synergistic optical/PET imaging combining
the sensitivity, quantification and limitless tissue penetration of PET with high
resolution and specificity of optical methods [102]. Cai et al. [103] reported the first
targeted dual-modality fluorescence/PET probe based on QDs. QDs and
RGD-functionalized QDs (RGD-QD) radiolabeled with
64 Cu via DOTA, with
labeling yields greater than 90% for both. With small-animal PET and NIRF
imaging in athymic nude mice, it was possible to observe a relatively high uptake of
QDs in the liver, spleen, lymph nodes, and bone marrow. The tumor uptake of the
two QD compounds was significantly different at all time points studied, except at
1 h p.i. (Fig. 2.5a).
64 Cu–DOTA–QD showed an uptake less than 1%ID/g in the
tumor tissue, suggesting low EPR effect, while active targeting (
64 Cu–DOTA–QD–
RGD) lead to a significantly higher tumor uptake (2.2 ± 0.3, 4.0 ± 1.0, and
4.3 ± 0.5%ID/g at 5, 18, and 25 h after injection, respectively) [103]. From that
point forward, several other studies have demonstrated the use of radiolabeled
QDs for tumor-targeted PET imaging as well as for multi-modality purposes
[97, 104–109].
Although the majority of studies make use of chelators, the stability of
chelator-based radiolabeled moieties in living animals can be a problem. For
example, in the study by Cai et al. [103], PET and NIR fluorescence imaging data
of mice injected with
64 Cu-labeled NIR QDs, were in good agreement with each
other at earlier time points of investigation, after which the distribution of
64 Cu
(PET) and the QDs (optical imaging) showed significant differences [103, 105].
Therefore, efforts have been made in order to achieve a chelator-free QD radiolabeling strategy. Intrinsic radiolabeling allows a variety of radionuclides to be
incorporated into the QDs, such as those of
64 Cu,
111 In,
59 Zn,
81 Se and others [18].
Sun et al. [110] designed self-illuminating chelator-free
64 Cu radiolabeled QDs, and
evaluated their Cerenkov luminescence and PET imaging capability in vivo. Ion
exchange between
64 Cu
+ and the original cation was used to trap
64 Cu into ionic
QDs, and nearly 100% radiolabeling yield and high radiostability were achieved. In
vivo PET imaging studies in U87MG tumor-bearing mice showed *5% ID/g
uptake in the tumor (1 h p.i.) that increased and peaked to 12.7% ID/g at 17 h p.i
and over 10%ID/g remained in the tumor tissue at the 42 h time point. Cerenkov
resonance energy transfer (CRET) imaging showed similar pattern with high tumor
uptake, suggesting the feasibility of using
64 Cu-doped QDs for both CRET and PET
imaging (Fig. 2.5b, c). Other papers on intrinsically radiolabeled QDs have been
published [18, 20, 111, 112].
While CdSe-based QDs have been widely investigated, their use in the clinical
settings is hampered by limitations such as toxicity of Cd ions in the core of QDs,
heterogeneous biodistribution profiles and concerns about the metabolism and
clearance behavior of the QDs [93]. An interesting paper regarding renal clearance
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
25
imaging were in agreement with previously published papers [101].
Following a research trend, several studies have been reported indicating that
QDs can provide a multifunctional nanoplatform for multimodality imaging and
therapy that is especially suitable for synergistic optical/PET imaging combining
the sensitivity, quantification and limitless tissue penetration of PET with high
resolution and specificity of optical methods [102]. Cai et al. [103] reported the first
targeted dual-modality fluorescence/PET probe based on QDs. QDs and
RGD-functionalized QDs (RGD-QD) radiolabeled with
64 Cu via DOTA, with
labeling yields greater than 90% for both. With small-animal PET and NIRF
imaging in athymic nude mice, it was possible to observe a relatively high uptake of
QDs in the liver, spleen, lymph nodes, and bone marrow. The tumor uptake of the
two QD compounds was significantly different at all time points studied, except at
1 h p.i. (Fig. 2.5a).
64 Cu–DOTA–QD showed an uptake less than 1%ID/g in the
tumor tissue, suggesting low EPR effect, while active targeting (
64 Cu–DOTA–QD–
RGD) lead to a significantly higher tumor uptake (2.2 ± 0.3, 4.0 ± 1.0, and
4.3 ± 0.5%ID/g at 5, 18, and 25 h after injection, respectively) [103]. From that
point forward, several other studies have demonstrated the use of radiolabeled
QDs for tumor-targeted PET imaging as well as for multi-modality purposes
[97, 104–109].
Although the majority of studies make use of chelators, the stability of
chelator-based radiolabeled moieties in living animals can be a problem. For
example, in the study by Cai et al. [103], PET and NIR fluorescence imaging data
of mice injected with
64 Cu-labeled NIR QDs, were in good agreement with each
other at earlier time points of investigation, after which the distribution of
64 Cu
(PET) and the QDs (optical imaging) showed significant differences [103, 105].
Therefore, efforts have been made in order to achieve a chelator-free QD radiolabeling strategy. Intrinsic radiolabeling allows a variety of radionuclides to be
incorporated into the QDs, such as those of
64 Cu,
111 In,
59 Zn,
81 Se and others [18].
Sun et al. [110] designed self-illuminating chelator-free
64 Cu radiolabeled QDs, and
evaluated their Cerenkov luminescence and PET imaging capability in vivo. Ion
exchange between
64 Cu
+ and the original cation was used to trap
64 Cu into ionic
QDs, and nearly 100% radiolabeling yield and high radiostability were achieved. In
vivo PET imaging studies in U87MG tumor-bearing mice showed *5% ID/g
uptake in the tumor (1 h p.i.) that increased and peaked to 12.7% ID/g at 17 h p.i
and over 10%ID/g remained in the tumor tissue at the 42 h time point. Cerenkov
resonance energy transfer (CRET) imaging showed similar pattern with high tumor
uptake, suggesting the feasibility of using
64 Cu-doped QDs for both CRET and PET
imaging (Fig. 2.5b, c). Other papers on intrinsically radiolabeled QDs have been
published [18, 20, 111, 112].
While CdSe-based QDs have been widely investigated, their use in the clinical
settings is hampered by limitations such as toxicity of Cd ions in the core of QDs,
heterogeneous biodistribution profiles and concerns about the metabolism and
clearance behavior of the QDs [93]. An interesting paper regarding renal clearance
2 Exogenous Radionanomedicine: Inorganic Nanomaterials
25