Show simple item record

dc.contributor.authorRusckowski, Mary
dc.contributor.authorQu, Timothy
dc.contributor.authorChang, F.
dc.contributor.authorHnatowich, Donald J.
dc.date2022-08-11T08:09:49.000
dc.date.accessioned2022-08-23T16:44:39Z
dc.date.available2022-08-23T16:44:39Z
dc.date.issued1997-12-24
dc.date.submitted2008-06-18
dc.identifier.citation<p>Cancer. 1997 Dec 15;80(12 Suppl):2699-705.</p>
dc.identifier.issn0008-543X (Print)
dc.identifier.pmid9406727
dc.identifier.urihttp://hdl.handle.net/20.500.14038/40543
dc.description.abstractOne goal of this investigation was to develop a polymer conjugated with multiple copies of peptide nucleic acid (PNA) and with pharmacokinetic properties suitable for applications in vivo. The second goal was to establish whether the multiple copies of PNA on the polymer could be targeted by hybridization in vitro and in vivo with 99mTc-labeled complementary PNA (cPNA). If successful, this approach could then be considered in further investigations as an alternative to existing pretargeting approaches because of the potential for signal amplification in the target. A 80 KDa poly(methyl vinyl ether-alt-maleic acid) (PA) polymer was conjugated with multiple copies of PNA and with multiple copies of poly(ethylene glycol) (PEG) by reacting the NHS derivative of PA with the amine derivatives of PNA and PEG. Using 99mTc-MAG3-cPNA, targeting of PNA-PA-PEG was studied in vitro and in vivo in inflammation and tumor mouse models, in both cases relying upon nonspecific diffusion for localization. In addition, cPNA-avidin was considered as a clearing agent with biotinylated PNA-PAPEG. About 80 PNAs could be conjugated to PA provided that about 200 PEGs were also conjugated to raise the aqueous solubility of the PNA-PA-PEG polymer lowered by the addition of the PNAs. About 70% of the PNAs on this polymer in vitro either in solution or attached to beads could be successfully targeted with 99mTc-cPNA. In both the inflammation and tumor mouse models, between 35 and 60% of these PNAs could be targeted in the lesions. The advantage of amplification was evident when less favorable results were obtained with PNA-PA-PEG conjugated with only six PNAs. We conclude that amplification can be achieved in vivo using polymers of PNA followed by radiolabeled complementary PNA and that the application of pretargeting using polymers of PNA for amplification can improve localization.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9406727&dopt=Abstract">Link to article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1021/bc0100307
dc.subjectAnimals
dc.subjectEscherichia coli Infections
dc.subjectIsotope Labeling
dc.subjectMale
dc.subjectMice
dc.subjectNeoplasms, Experimental
dc.subjectNucleic Acids
dc.subjectPeptides
dc.subjectTechnetium
dc.subjectTissue Distribution
dc.subjectAnimal Experimentation and Research
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.subjectNeoplasms
dc.subjectPathological Conditions, Signs and Symptoms
dc.titlePretargeting with Amplification Using Polymeric Peptide Nucleic Acid
dc.typeArticle
dc.source.journaltitleCancer
dc.source.volume80
dc.source.issue12 Suppl
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/335
dc.identifier.contextkey533043
html.description.abstract<p>One goal of this investigation was to develop a polymer conjugated with multiple copies of peptide nucleic acid (PNA) and with pharmacokinetic properties suitable for applications in vivo. The second goal was to establish whether the multiple copies of PNA on the polymer could be targeted by hybridization in vitro and in vivo with 99mTc-labeled complementary PNA (cPNA). If successful, this approach could then be considered in further investigations as an alternative to existing pretargeting approaches because of the potential for signal amplification in the target. A 80 KDa poly(methyl vinyl ether-alt-maleic acid) (PA) polymer was conjugated with multiple copies of PNA and with multiple copies of poly(ethylene glycol) (PEG) by reacting the NHS derivative of PA with the amine derivatives of PNA and PEG. Using 99mTc-MAG3-cPNA, targeting of PNA-PA-PEG was studied in vitro and in vivo in inflammation and tumor mouse models, in both cases relying upon nonspecific diffusion for localization. In addition, cPNA-avidin was considered as a clearing agent with biotinylated PNA-PAPEG. About 80 PNAs could be conjugated to PA provided that about 200 PEGs were also conjugated to raise the aqueous solubility of the PNA-PA-PEG polymer lowered by the addition of the PNAs. About 70% of the PNAs on this polymer in vitro either in solution or attached to beads could be successfully targeted with 99mTc-cPNA. In both the inflammation and tumor mouse models, between 35 and 60% of these PNAs could be targeted in the lesions. The advantage of amplification was evident when less favorable results were obtained with PNA-PA-PEG conjugated with only six PNAs. We conclude that amplification can be achieved in vivo using polymers of PNA followed by radiolabeled complementary PNA and that the application of pretargeting using polymers of PNA for amplification can improve localization.</p>
dc.identifier.submissionpathoapubs/335
dc.contributor.departmentDepartment of Radiology
dc.contributor.departmentDepartment of Nuclear Medicine
dc.source.pages2699-705


This item appears in the following Collection(s)

Show simple item record