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Synthesis and Biologic Evaluation of 64Cu-Labeled Rhenium-Cyclized {alpha}-MSH Peptide Analog Using a Cross-Bridged Cyclam Chelator

Lihui Wei1, Clayton Butcher2, Yubin Miao2, Fabio Gallazzi2, Thomas P. Quinn2, Michael J. Welch1 and Jason S. Lewis1

1 Division of Radiological Sciences, Mallinckrodt Institute of Radiology and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri; and 2 Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri


Figure 1
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FIGURE 1.  Structures of CBTE2A-ReCCMSH(Arg11) and DOTA-ReCCMSH(Arg11).

 

Figure 2
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FIGURE 2.  Comparison of biodistribution of 64Cu-DOTA-ReCCMSH(Arg11) (185 kBq [5 µCi], 16 ng, n = 4; {square}) (8) and 64Cu-CBTE2A-ReCCMSH(Arg11) (185 kBq [5 µCi], 16 ng, n = 5; {blacktriangleup}) in B16/F1 tumor-bearing C57 mice at 2 h after injection. Data are presented as %ID/g ± SD. Note differences in y-axis scales.

 

Figure 3
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FIGURE 3.  Biodistribution comparison of 64Cu-CBTE2A-ReCCMSH(Arg11) with high SA (2 ng) and low SA (16 ng) and effect of preinjection of 15 mg D-lysine (2 h after injection).

 

Figure 4
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FIGURE 4.  Selected tumor-to-organ ratios for 64Cu-DOTA-ReCMSH(Arg11) (8), 64Cu-CBTE2A-ReCCMSH(Arg11) with lower and higher SA, and 86Y-DOTA-ReCCMSH(Arg11) (8) at 2 h in C57 mice implanted with B16/F1 tumors. (P = ReCCMSH(Arg11).)

 

Figure 5
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FIGURE 5.  (A) Coronal images of C57 mice implanted with B16/F1 tumors at 30 min and at 2, 4, and 24 h after tail vein injection of 5.55 MBq (150 µCi) (500 ng) of 64Cu-CBTE2A-ReCCMSH(Arg11). At each time point a mouse that received blockade (left) was coimaged with a mouse that did not receive blockade (right). Blockade mouse received 20 µg of CBTE2A-ReCCMSH(Arg11). Images shown are 1-mm slices, with animal in supine position, and slices shown are through center of tumor volume. As tumors do not grow in exactly the same location from animal to animal, slices may show different tissues in addition to tumors. PET images show that administration of a blockade dose substantially reduces tumor uptake of the agent by such an extent that tumor is difficult to delineate. It is also evident that background accumulation is very low, resulting in excellent tumor contrast. T = tumor; K = kidney. (B) microPET/CT coregistered images of B16/F1 tumor-bearing mice 2 h after tail vein injection of 5.5 MBq (500 ng) of 64Cu-CBTE2A-ReCCMSH(Arg11). Images shown are 1-mm slices and slices shown are through center of tumor volume.

 

Figure 6
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FIGURE 6.  SUV data obtained for PET analysis of 64Cu-CBTE2A-ReCCMSH(Arg11) (500 ng) in C57 mice implanted with B16/F1 tumors. Shown are SUVs of uptakes in tumor (A), liver (B), and kidney (C). SUVs for tumor (A) are low due to mass of peptide administered compared with that in biodistribution study (16 ng).

 





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