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    Tumor pretargeting in mice using (99m)Tc-labeled morpholino, a DNA analog

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    Authors
    Liu, Guozheng
    Mang'era, Kennedy O.
    Liu, Ning
    Gupta, Suresh
    Rusckowski, Mary
    Hnatowich, Donald J.
    UMass Chan Affiliations
    Department of Radiology, Division of Nuclear Medicine
    Document Type
    Journal Article
    Publication Date
    2002-03-09
    Keywords
    Animals
    Carcinoembryonic Antigen
    Colonic Neoplasms
    Mice
    Mice, Nude
    Molecular Weight
    Morpholines
    Neoplasm Transplantation
    Oligonucleotides
    Organotechnetium Compounds
    use
    Radiopharmaceuticals
    Technetium Tc 99m Mertiatide
    Tissue Distribution
    Tumor Cells, Cultured
    Life Sciences
    Medicine and Health Sciences
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    Link to Full Text
    http://jnm.snmjournals.org/content/43/3/384.full.pdf+html
    Abstract
    Over the past several years, investigators in this laboratory and elsewhere have been studying tumor localization by pretargeting with streptavidin and biotin or with avidin and biotin. Despite encouraging results, difficulties related to endogenous biotin and the immunogenicities of streptavidin and avidin have made a search for alternative strategies sensible. Recently, we have considered the use of DNAs and peptide nucleic acids for this purpose because oligomers can have hybridization affinities equivalent to that of biotin for streptavidin or avidin without the associated difficulties. We now report on the use of a morpholino (MORF), another commercially available synthetic oligomer, for pretargeting applications. MORFs support the nitrogenous bases by nonionic phosphorodiamidate linkages and, besides being nuclease resistant, can display good water solubility. METHODS: An 18mer MORF and its 18mer complementary MORF (cMORF) were obtained with a primary amine through a 3-member alkyl linker on the 3' equivalent end. An anti--carcinoembryonic antigen IgG antibody (MN14) was conjugated with MORF, whereas cMORF was conjugated with N-hydroxysuccinimide-mercaptoacetyltriglycine (MAG3) to permit radiolabeling with (99m)Tc. The biodistribution of labeled cMORF was first evaluated in normal CD-1 mice. Subsequently, nude mice bearing LS174T tumors received 50 microg conjugated antibody 48 h before the administration of 1.0 microg (7.4 MBq) (99m)Tc-MAG3-cMORF. Control animals received the labeled cMORF without prior administration of the antibody. A clearing step was not used. RESULTS: Biodistributions in normal mice showed that (99m)Tc-MAG3-cMORF was excreted rapidly through the kidneys, with only 7 percentage injected dose (%ID) remaining within the whole body (excluding urine) at 3 h. In tumor-bearing mice at 24 h, only 11 %ID of the radioactivity remained in the whole body of study animals, and of this amount, 2 %ID/g was in tumor tissue. The sites with the highest %ID were the kidneys, at 4 %ID/g, and the blood, at 0.5 %ID/g; all other organs had <1 >%ID/g. At the same time, values for the control animals were 5 %ID (whole body), 0.05 %ID/g (tumor), and 3 %ID (kidneys). All images reflected high uptake in the tumors and low uptake in the normal tissues of the study mice. CONCLUSION: Pretargeting using MORFs was effective in a mouse tumor model.
    Source
    J Nucl Med. 2002 Mar;43(3):384-91.
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/38320
    PubMed ID
    11884499
    Related Resources
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    UMass Chan Faculty and Researcher Publications
    Radiology Publications

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