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A 2-Helix Small Protein Labeled with ⁶⁸Ga for PET Imaging of HER2 Expression

¹ Molecular Imaging Program at Stanford (MIPS), Department of Radiology and Bio-X Program, Stanford University, Stanford, California; and ² Global Research, General Electric Co., Niskayuna, New York

View larger version (43K): [in this window] [in a new window]   FIGURE 1.  Three-helix Affibody and 2-helix protein scaffold–based PET probes for HER2 imaging. Black dots and red regions indicate amino acid residues responsible for receptor binding.

View larger version (6K): [in this window] [in a new window]   FIGURE 2.  HPLC radiochromatograms of purified 68Ga-DOTA-MUT-DS (A) and radiolabeled probe after 40 min of incubation with mouse serum (B).

View larger version (15K): [in this window] [in a new window]   FIGURE 3.  Biosensor binding studies of DOTA-MUT-DS.

View larger version (10K): [in this window] [in a new window]   FIGURE 4.  Cell uptake of 68Ga-DOTA-MUT-DS in SKOV3 cells over time at 37°C with or without nonradioactive Affibody molecule ZHER2:477. All results are expressed as mean of triplicate measurement ± SD.

View larger version (31K): [in this window] [in a new window]   FIGURE 5.  Representative decay-corrected coronal (top) and transaxial (bottom) PET images of nude mice bearing SKOV3 tumor on right shoulder at 0.5, 1, and 2 h after tail vein injection of 68Ga-DOTA-MUT-DS: nontreated group (A) and treated group (B) (images were acquired after 24 h of treatment with 17-DMAG; arrows indicate location of tumors). (C) Quantification analysis of tumor uptake before and after 17-DMAG treatment. Data are expressed as mean of 3 mice ± SD.

View larger version (41K): [in this window] [in a new window]   FIGURE 6.  Representative Western blot detection of HER2 expression in tumor tissue samples. SKOV3 tumor homogenates were prepared and 50 µg of protein were detected with rabbit antihuman HER2 monoclonal antibody. L1 = lane 1, nontreated tumor; L2 = lane 2, tumor treated with 17-DMAG.