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111In-Benzyl-DTPA–ZHER2:342, an Affibody-Based Conjugate for In Vivo Imaging of HER2 Expression in Malignant Tumors

Vladimir Tolmachev1,2, Fredrik Y. Nilsson1,2, Charles Widström3, Karl Andersson1, Daniel Rosik2, Lars Gedda1, Anders Wennborg2 and Anna Orlova1,2

1 Division of Biomedical Radiation Sciences, Uppsala University, Uppsala, Sweden; 2 Affibody AB, Bromma, Sweden; and 3 Department of Hospital Physics, Uppsala University Hospital, Uppsala, Sweden


Figure 1
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  		FIGURE 1.  Amino acid sequence of ZHER2:342. HER2-binding site is formed by helices 1 and 2. Helix 3 provides structural rigidity of Affibody molecules.

 

Figure 2
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  		FIGURE 2.  Cell-associated 111In radioactivity as function of time after interrupted incubation of SKOV-3 cells with 111In-benzyl-DTPA–ZHER2:342. Cell-associated radioactivity at time zero after interrupted incubation was considered as 100%. Data are presented as mean ± SD (n = 3). Error bars are not evident because they are smaller than • symbols.

 

Figure 3
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  		FIGURE 3.  Specificity of 111In-benzyl-DTPA–ZHER2:342 uptake in vivo. One group of animals was preinjected with 375 µg ZHER2:342 to saturate HER2 receptors 1 h before injection of radiolabeled conjugate. All animals were injected with 1 µg 111In-benzyl-DTPA–ZHER2:342. Data are mean ± SD (n = 4).

 

Figure 4
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  		FIGURE 4.  Tumor-to-organ ratio of 111In-benzyl-DTPA–ZHER2:342 in tumor-bearing nude mice. Ratios are calculated from animals of Table 1. Data are mean ± SD (n = 4).

 

Figure 5
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  		FIGURE 5.  Imaging of HER2 expression in SKOV-3 xenografts in BALB/c nu/nu mice using 111In-benzyl-DTPA–ZHER2:342. Planar {gamma}-camera images were collected 4 h after administration of 111In-benzyl-DTPA–ZHER2:342. Tumors (arrows) were clearly visualized.

 




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