Figure 1.
Metal complexes of the chelators 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA), 1,4,7,10-tetraazacylododecane-1,4,7,10-tetraacetic acid (DOTA), and 1-(1,3-carboxypropyl)-1,4,7-triazacyclononane-4.7-diacetic acid (NODAGA) conjugated to N-terminal amino group via amide bonds.
Table 1.
Biophysical characteristics of the Affibody conjugates [22].
Table 2.
Labeling yield (decay corrected), radiochemical purity and stability of 68Ga-labeled Affibody molecules.
Figure 2.
In vitro specificity test of 68Ga-NODAGA-ZHER2:S1 (A), 68Ga-NOTA-ZHER2:S1 (B) and 68Ga-DOTA-ZHER2:S1 (C) binding to HER2 expressing SKOV-3 cells.
Dishes containing cells were incubated with 27 pM radiolabeled conjugated. One group of dishes was pre-saturated with 1000-fold excesses of non-labeled ZHER2:S1 to block the binding site of HER2. Cell-associated radioactivity was calculated as percentage of total added radioactivity. Data are presented as mean values for three cell dishes and standard deviations.
Figure 3.
Cellular processing of 68Ga-NODAGA-ZHER2:S1, 68Ga-NOTA-ZHER2:S1 and 68Ga-DOTA-ZHER2:S1 by HER2-expressing cells SKOV-3 in vitro.
Cells were incubated with labeled compound at 37°C. Cell bound activity is normalized to the maximum uptake. Data are presented as mean values for three cell dishes and standard deviations. Error bars might be smaller than the symbols.
Figure 4.
Specificity of targeting of SKOV-3 xenografts in BALB/C nu/nu mice using 68Ga-DOTA-ZHER2:S1, 68Ga-NOTA-ZHER2:S1 and 68Ga-NODAGA-ZHER2:S1 at 1h after injection.
The total injected radiolabeled peptide dose per mouse was 3 µg (0.42 nmol). The blocked group was subcutaneously pre-injected with an excess amount (1000 µg, 150 nmol) of non-labelled ZHER2∶342 to saturate binding sites of HER2. Results are expressed as percentage of injected activity per gram of tissue (%IA/g) and presented as mean values for four mice and standard deviations. Uptake of radioactivity was significant lower (p<0.0005) for pre-saturated SKOV-3 tumors.
Table 3.
Comparative biodistribution of NODAGA-ZHER2:S1, NOTA-ZHER2:S1 and DOTA-ZHER2:S1 labelled with gallium-68 and indium-111 after intravenous injection in female BALB/C nu/nu mice bearing SKOV-3 xenografts.
Table 4.
Tumor-to-organ ration data 2h after injection for NODAGA-ZHER2:S1, NOTA-ZHER2:S1 and DOTA-ZHER2:S1 in mice bearing SKOV-3 xenografts.
Figure 5.
MicroPET/CT imaging of HER2 expression in SKOV3 xenografts in BALB/C nu/nu mice using 68Ga-NODAGA-ZHER2:S1.
The image was acquired 2 h after administration of the tracer. Arrows point at tumor (T) and kidneys (K).