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First published online February 20, 2008, 10.2967/jnumed.107.045138
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Molecular Imaging of bcl-2 Expression in Small Lymphocytic Lymphoma Using 111In-Labeled PNA–Peptide Conjugates

Fang Jia1, Said Daibes Figueroa2, Fabio Gallazzi3, Baghavathy S. Balaji1, Mark Hannink4, Susan Z. Lever5, Timothy J. Hoffman2,6 and Michael R. Lewis1,2,7,8

1 Department of Veterinary Medicine and Surgery, University of Missouri-Columbia, Columbia, Missouri; 2 Research Service, Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri; 3 Molecular Biology Program, University of Missouri-Columbia, Columbia, Missouri; 4 Department of Biochemistry, University of Missouri-Columbia, Columbia, Missouri; 5 Department of Chemistry, University of Missouri-Columbia, Columbia, Missouri; 6 Department of Internal Medicine, University of Missouri-Columbia, Columbia, Missouri; 7 Department of Radiology, University of Missouri-Columbia, Columbia, Missouri; and 8 Nuclear Science and Engineering Institute, University of Missouri-Columbia, Columbia, Missouri


Figure 1
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  		FIGURE 1.  Structures and synthesis of DOTA–PNA–peptide conjugates.

 

Figure 2
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  		FIGURE 2.  Somatostatin receptor binding of 111In-DOTA-anti-bcl-2-PNA-Tyr3-octreotate and 111In-DOTA-Tyr3-octreotate in Mec-1 cells.

 

Figure 3
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  		FIGURE 3.  Uptake and blocking of 111In-DOTA–PNA–peptide conjugates in Mec-1 cells (n = 3).

 

Figure 4
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  		FIGURE 4.  Internalization of 111In-DOTA–PNA–peptide conjugates in Mec-1 cells (n = 3).

 

Figure 5
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  		FIGURE 5.  Efflux of 111In-DOTA–PNA–peptide conjugates in Mec-1 cells (n = 3).

 

Figure 6
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  		FIGURE 6.  Western blot analysis of bcl-2 protein synthesis. Lane 1, untreated control; lane 2, cells treated with compound 1; lane 3, untreated control; lane 4, cells treated with compound 2; lane 5, cells treated with compound 3.

 

Figure 7
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  		FIGURE 7.  (Top) MicroSPECT/CT images of 111In-DOTA–PNA–peptide conjugates in Mec-1–bearing SCID mice (n = 3). (A) 111In-DOTA-Tyr3-octreotate (1 h). (B) 111In-DOTA-anti-bcl-2-PNA-Tyr3-octreotate (48 h). (C) 111In-DOTA-nonsense-PNA-Tyr3-octreotate (48 h). (D) 111In-DOTA-anti-bcl-2-PNA-Ala[3,4,5,6] (48 h). (Bottom) Corresponding transaxial slices through the centers of the tumors.

 




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