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dc.contributor.authorLiu, Guozheng
dc.contributor.authorMang'era, Kennedy O.
dc.contributor.authorLiu, Ning
dc.contributor.authorGupta, Suresh
dc.contributor.authorRusckowski, Mary
dc.contributor.authorHnatowich, Donald J.
dc.date2022-08-11T08:09:32.000
dc.date.accessioned2022-08-23T16:34:23Z
dc.date.available2022-08-23T16:34:23Z
dc.date.issued2002-03-09
dc.date.submitted2009-03-10
dc.identifier.citationJ Nucl Med. 2002 Mar;43(3):384-91.
dc.identifier.issn0161-5505 (Print)
dc.identifier.pmid11884499
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38320
dc.description.abstractOver 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.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=11884499&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://jnm.snmjournals.org/content/43/3/384.full.pdf+html
dc.subjectAnimals
dc.subjectCarcinoembryonic Antigen
dc.subjectColonic Neoplasms
dc.subjectMice
dc.subjectMice, Nude
dc.subjectMolecular Weight
dc.subjectMorpholines
dc.subjectNeoplasm Transplantation
dc.subjectOligonucleotides
dc.subjectOrganotechnetium Compounds
dc.subjectuse
dc.subjectRadiopharmaceuticals
dc.subjectTechnetium Tc 99m Mertiatide
dc.subjectTissue Distribution
dc.subjectTumor Cells, Cultured
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleTumor pretargeting in mice using (99m)Tc-labeled morpholino, a DNA analog
dc.typeJournal Article
dc.source.journaltitleJournal of nuclear medicine : official publication, Society of Nuclear Medicine
dc.source.volume43
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1189
dc.identifier.contextkey770167
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/1189
dc.contributor.departmentDepartment of Radiology, Division of Nuclear Medicine
dc.source.pages384-91


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