TcEC Targeted Imaging Agents Glycolysis Targets

Owing to the structural similarity between glucosamine (2-amino deoxyglucose) and FDG (2-fluoro deoxyglucose), it was predicted that 99mTc-EC-glucosamine (EC-DG) could act as the SPECT analog of FDG-PET. The chemical structure of

99mTc-C-DG is shown in Figure 1. The labeling efficiency of this adduct is 95% to 100%. However,99mTc-EC-DG is also predicted to be taken up by the nucleic acid synthesis. To demonstrate whether 99mTc-EC-DG was involved in DNA/RNA incorporation, thymidine incorporation assays were conducted with EC-DG, FDG, and glucose. Tissue distribution, dosimetry, autoradiographic, and gamma scintigraphic imaging studies of 99mTc-EC-DG and 18F-FDG were conducted in tumor bearing animal models. Tumor/nontarget tissue count density ratios were calculated from the corresponding %ID/g values.

Biodistribution studies with 99mTc-EC-DG revealed that tumor/brain and tumor/muscle ratios of 99mTc-EC-DG in rodents were higher than 18F-FDG (57). Data obtained from thymidine incorporation assays indicated that EC-DG and glucose was involved in cell nuclei activity whereas FDG was not (Fig. 2). In vivo imaging studies showed that changes in tumor volume could be monitored with 99mTc-EC-DG (Figs. 3-5). Compared to the images of nontargeted 99mTc-EC (control), the tumor was visualized quite clearly only with 99mTc-EC-DG (Fig. 6). A xenograft human uterine sarcoma implanted in nude mice could be visualized by autoradiography with 99mTc-EC-DG but not controls (Figs. 7 and 8). Compared to 18F-FDG, less brain or myocardial radioactivity was observed with 99mTc-EC-DG groups. These findings support the potential use of 99mTc-EC-DG as a functional imaging agent.

Synthesis of 99mTc-EC-DG

Synthesis of 99mTc-EC-DG

"mTc-EC-deoxy glucose

Figure 1 Synthetic procedure for conjugation of D-glucosamine to ethlenedicysteine (EC). Stablizing/activating agents (1) and (2) radioisotope/reducing agent are then added to form radiolabeled EC-DG.

"mTc-EC-deoxy glucose

Figure 1 Synthetic procedure for conjugation of D-glucosamine to ethlenedicysteine (EC). Stablizing/activating agents (1) and (2) radioisotope/reducing agent are then added to form radiolabeled EC-DG.

Figure 2 Thymidine incorporation assay indicated that both EC-DG and D-glucose exhibited similar DNA/RNA incorporation values. FDG showed decreased cell nuclei activity in a dose-dependent manner. The findings suggest that EC-DG is a more tumor-specific agent than FDG.
Figure 3 On day 7 postinoculation of tumor cells, planar scintigraphy of 99mTc-EC-DG in breast tumor-bearing rats (100 mCi/rat, IV) was conducted at 90 minutes. Uptake in the tumor (a and c) is greater than that of muscle tissue (c and d) by using an eZ-scope. (See color insert)

Breast minor Day 10

Breast minor Day 10

Figure 4 On day 10 postinoculation of tumor cells, planar scintigraphy of Tc-EC-DG in breast tumor-bearing rats (100 mCi/rat, IV) shows the tumors (1 cm) well. The imaging study was conducted at 90 minutes. Uptake in the tumor (a and c) is greater than that in muscle tissue by using an eZ-scope. (See color insert.)

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