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Imaging with ^99mTc ECDG Targeted at the Multifunctional Glucose Transport System: Feasibility Study with Rodents¹

¹ From the Divisions of Diagnostic Imaging (D.J.Y., C.G.K., A.A., D.F.Y., C.S.O., J.L.B., J.J.W., E.E.K., D.A.P.) and Radiation Oncology (N.R.S.), University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030. From the 2001 RSNA scientific assembly. Received November 9, 2001; revision requested January 7, 2002; final revision received May 16; accepted June 18. The animal research and nuclear magnetic resonance facility used in this study was supported by M.D. Anderson Cancer Center (Cancer Center Support Grant) grant NIH CA-16672. Supported in part by Cell Point Research Fund. Address correspondence to D.J.Y. (e-mail: dyang@di.mdacc.tmc.edu).

View larger version (26K): [in a new window]   Figure 1. Synthesis of 99mTc ECDG: D-glucosamine is reacted with ethylenedicysteine in the presence of coupling agents, and tin (II) chloride and pertechnetate were added to the solution. MW = molecular weight.

View larger version (20K): [in a new window]   Figure 2. ECDG (98.7 mg) was labeled with 100 mCi (3,700 MBq) of NaTcO4 in the presence of stannous chloride and spotted on an instant thin-layer chromatography strip. The eluant used was 1 mol/L of ammonium acetate with methanol (4:1). The radio-thin-layer chromatography data shown indicate 98.5% radiochemical purity. The data shown on the two axes represent counts of 99mTc ECDG and length of the eluant migrated.

View larger version (21K): [in a new window]   Figure 3. Graph depiction of the results of hexokinase assay performed to determine the phosphorylation of ECDG. ECDG phosphorylation was determined by means of coupling hexokinase activity with the reduction of nicotinamide adenine dinucleotide (NAD) to its reduced form (NADH). The absorption of reduced-form nicotinamide adenine dinucleotide occurs at an ultraviolet wavelength of 340-350 nm; this indicates positive glucose phosphorylation activity (341.5 nm). The absorption of nonreduced nicotinamide adenine dinucleotide occurs at an ultraviolet wavelength of 302.5 nm.

View larger version (20K): [in a new window]   Figure 4. Bar graph illustrates the in vitro cellular uptake of 99mTc ECDG (EC-DG) and 18F FDG. Graph data show that there was a markedly increased uptake of 99mTc ECDG and 18F FDG as a function of time compared with the uptake of 99mTc ethylenedicysteine (EC), the control agent. Asterisks indicate that there was a significant (P < .05, Student pair t test) difference between 99mTc ECDG uptake and 18F FDG uptake during the same interval. Data are reported as means ± standard errors of the mean in the three agent groups. Data points were calculated as percentages of uptake.

View larger version (18K): [in a new window]   Figure 5. Bar graph illustrates the in vitro cellular uptake of 99mTc ECDG when glucose (GLU) was administered. Graph data show that there was a markedly decreased uptake of 99mTc ECDG as a function of D-glucose concentration compared with the uptake as a function of L-glucose concentration. Asterisks indicate that there was a significant (P < .05, Student pair t test) difference between the L-glucose- and D-glucose-loaded groups at equal concentrations. Data are reported as means ± standard errors of the mean in the three glucose dose groups. Data points were calculated as percentages of 99mTc ECDG uptake.

View larger version (42K): [in a new window]   Figure 6. Data plotted to illustrate the intravenous (i.v.) administration of ECDG (EC-DG) and glucosamine in rats show increasing blood glucose levels as a function of time up to nearly 210 minutes after injection. Intravenous administration of ECDG and insulin caused a marked decrease in blood glucose levels.

View larger version (38K): [in a new window]   Figure 7. Planar scintigrams of 99mTc ECDG (300 µCi [11.1 MBq] per rat administered intravenously) uptake in breast tumor-bearing rats demonstrate that small (3-mm) and medium-sized (med, 6-mm) neoplasms could be imaged up to 2 hours after radionuclide administration. Arrows in the left image point to small and medium-sized tumors. The mean tumor-to-nontumor (opposite leg) ROI ratios determined immediately, 30 minutes, and 2 hours after 99mTc ECDG injection were 1.70 ± 0.21, 1.58 ± 0.30, and 1.82 ± 0.07, respectively, for the small tumors and 2.36 ± 0.06, 2.41 ± 0.10, and 2.88 ± 0.10, respectively, for the medium-sized tumors. Uptake was also observed in the heart (H), liver, kidneys, and bladder.

View larger version (34K): [in a new window]   Figure 8. Planar scintigrams of 99mTc ethylenedicysteine (99mTc-EC) and 99mTc ECDG (99mTc-EC-DG) uptake in breast tumor-bearing rats (300 µCi [11.1 MBq] per rat administered intravenously) demonstrate that the tumor could be better imaged at 99mTc ECDG scintigraphy. Arrows point to tumors (T).

View larger version (91K): [in a new window]   Figure 9. Planar scintigrams of 99mTc ECDG (99mTc-EC-DG) uptake (300 µCi [11.1 MBq] per rat administered intravenously) in breast tumor-bearing rats (three rats per agent group) obtained 30 minutes after injection demonstrate that pretreatment of the rats with FDG (middle image) or insulin (right image) affected the uptake of 99mTc ECDG. Arrow points to the tumor (T).