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Tumor Pretargeting in Mice Using 99mTc-Labeled Morpholino, a DNA Analog

Guozheng Liu, PhD;1, Kennedy Mang’era, PhD;1, Ning Liu, MD;1, Suresh Gupta, PhD;1, Mary Rusckowski, PhD;1 and Donald J. Hnatowich, PhD1

1 Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, Massachusetts



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  		FIGURE 1. Ultraviolet (UV, 260 nm) SE HPLC profiles of uncoupled, native cMORF (A) and MAG3-coupled cMORF (B) and radioactivity profile of 99mTc-labeled MAG3-cMORF (C).

 


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  		FIGURE 2. Ultraviolet (UV, 260 nm) SE HPLC profile of MN14-MORF (A), radioactivity profiles of labeled cMORF added to MN14-MORF at weight ratios of 0.04 µg/25 µg (B) and 0.25 µg/25 µg (C), and radioactivity profile of labeled cMORF added to native MN14 as control (D). Extent of labeled cMORF binding decreased as weight of labeled cMORF increased.

 


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  		FIGURE 3. Plot of data from saturation study shows variation in ratio of free labeled cMORF to labeled cMORF-MN14-MORF as increasing weights of labeled cMORF were added. Curve was extrapolated to origin to estimate average number of MORF groups per MN14 molecule.

 


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  		FIGURE 4. Radioactivity SE HPLC profiles of urine obtained at 3 h from control mouse receiving only labeled cMORF (A) and from study mouse receiving both MN14-MORF and labeled cMORF (B) and radiochromatograms, on same axes, of plasma obtained at 3 h from control mouse (C) and from study mouse (D). Results show that radioactivity in urine was present primarily as labeled cMORF, whereas in plasma, significant levels of radioactivity were present only in study mice and then only as labeled cMORF-MN14-MORF.

 


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  		FIGURE 5. Gamma camera images of LS174T tumor-bearing nude mice show whole-body anterior views obtained at 3 h (A) and 24 h (C) and, during repeated study after removal of urine, at 3 h (B). In each pair of images, study animal is on left and control animal is on right.

 




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