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dc.contributor.authorLiu, Guozheng
dc.contributor.authorDou, Shuping
dc.contributor.authorLiu, Yuxia
dc.contributor.authorWang, Yuzhen
dc.contributor.authorRusckowski, Mary
dc.contributor.authorHnatowich, Donald J.
dc.date2022-08-11T08:10:48.000
dc.date.accessioned2022-08-23T17:20:28Z
dc.date.available2022-08-23T17:20:28Z
dc.date.issued2011-12-21
dc.date.submitted2014-11-17
dc.identifier.citationBioconjug Chem. 2011 Dec 21;22(12):2539-45. doi: 10.1021/bc200366t. <a href="http://dx.doi.org/10.1021/bc200366t">Link to article on publisher's site</a>
dc.identifier.issn1043-1802 (Linking)
dc.identifier.doi10.1021/bc200366t
dc.identifier.pmid21985267
dc.identifier.urihttp://hdl.handle.net/20.500.14038/48309
dc.description.abstractWhile (188)Re has been used successfully in mice for tumor radiotherapy by MORF/cMORF pretargeting, previous radiolabeling of the amine-derivatized cMORF with (90)Y, a longer physical half-life nuclide, was not very successful. After developing a method involving a prepurification heating step during conjugation that increases labeling efficiency and label stability, the biodistribution of (90)Y-DOTA-Bn-SCN-cMORF ((90)Y-DOTA-cMORF) was measured in normal mice and in MORF-CC49 pretargeted mice that bear LS174T tumors. Absorbed radiation doses were then estimated and compared to those estimated for (188)Re. The pharmacokinetics of the (90)Y-DOTA-cMORF in normal mice and in the pretargeted nude mice was similar to that observed previously with (99m)Tc- and (188)Re-MAG(3)-cMORFs. While the (90)Y-DOTA-cMORF cleared rapidly from normal tissues, tumor clearance was very slow and tumor radioactivity accumulation was constant for at least 7 days such that the tumor/blood (T/B) ratio increased linearly from 6 to 25 over this period. Therefore, by extrapolation, normal tissue toxicities following administration of therapeutic doses of (90)Y may be comparable to that observed for (188)Re in which the T/B increased from 5 to 20. In conclusion, radiolabeling of DOTA-cMORF with (90)Y was improved by introducing a prepurification heating step during conjugation. The (90)Y-DOTA-cMORF provided a similar T/B ratio and biodistribution to that of (188)Re-MAG(3)-cMORF and was retained well in the tumor pretargeted with MORF-CC49. Because of the longer physical half-life, the T/NT absorbed radiation dose ratios were improved in most organs and especially in blood.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=21985267&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3244554/pdf/nihms332441.pdf
dc.subjectAnimals
dc.subjectHeterocyclic Compounds
dc.subjectMice
dc.subjectMice, Nude
dc.subjectMorpholinos
dc.subjectNeoplasms
dc.subjectOrganometallic Compounds
dc.subjectRadiopharmaceuticals
dc.subjectCancer Biology
dc.subjectMedicinal and Pharmaceutical Chemistry
dc.subjectMedicinal-Pharmaceutical Chemistry
dc.subjectOncology
dc.subjectRadiochemistry
dc.subjectRadiology
dc.subjectTherapeutics
dc.title90Y labeled phosphorodiamidate morpholino oligomer for pretargeting radiotherapy
dc.typeJournal Article
dc.source.journaltitleBioconjugate chemistry
dc.source.volume22
dc.source.issue12
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/radiology_pubs/42
dc.legacy.embargo2014-12-09T00:00:00-08:00
dc.identifier.contextkey6367422
html.description.abstract<p>While (188)Re has been used successfully in mice for tumor radiotherapy by MORF/cMORF pretargeting, previous radiolabeling of the amine-derivatized cMORF with (90)Y, a longer physical half-life nuclide, was not very successful. After developing a method involving a prepurification heating step during conjugation that increases labeling efficiency and label stability, the biodistribution of (90)Y-DOTA-Bn-SCN-cMORF ((90)Y-DOTA-cMORF) was measured in normal mice and in MORF-CC49 pretargeted mice that bear LS174T tumors. Absorbed radiation doses were then estimated and compared to those estimated for (188)Re. The pharmacokinetics of the (90)Y-DOTA-cMORF in normal mice and in the pretargeted nude mice was similar to that observed previously with (99m)Tc- and (188)Re-MAG(3)-cMORFs. While the (90)Y-DOTA-cMORF cleared rapidly from normal tissues, tumor clearance was very slow and tumor radioactivity accumulation was constant for at least 7 days such that the tumor/blood (T/B) ratio increased linearly from 6 to 25 over this period. Therefore, by extrapolation, normal tissue toxicities following administration of therapeutic doses of (90)Y may be comparable to that observed for (188)Re in which the T/B increased from 5 to 20. In conclusion, radiolabeling of DOTA-cMORF with (90)Y was improved by introducing a prepurification heating step during conjugation. The (90)Y-DOTA-cMORF provided a similar T/B ratio and biodistribution to that of (188)Re-MAG(3)-cMORF and was retained well in the tumor pretargeted with MORF-CC49. Because of the longer physical half-life, the T/NT absorbed radiation dose ratios were improved in most organs and especially in blood.</p>
dc.identifier.submissionpathradiology_pubs/42
dc.contributor.departmentDepartment of Radiology, Division of Nuclear Medicine
dc.source.pages2539-45


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