Source:http://linkedlifedata.com/resource/pubmed/id/16720238
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
4
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| pubmed:dateCreated |
2006-5-24
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| pubmed:abstractText |
Significant improvement of in vivo stability of 211At-labeled radioimmunoconjugates achieved upon employment of a recently reported new linker, succinimidyl N-2-(4-[211At]astatophenethyl)succinamate (SAPS), prompted additional studies of its chemistry. The 211At radiolabeling of succinimidyl N-2-(4-tributylstannylphenethyl)succinamate (1) was noted to decline after storage at -15 degrees C for greater than 6 months. Compound 1 was found to degrade via a ring closure reaction with the formation of N-2-(4-tributylstannylphenethyl)succinimide (3), and a modified procedure for the preparation of 1 was developed. The N-methyl structural analog of 1, succinimidyl N-2-(4-tributylstannylphenethyl)-N-methyl succinamate (SPEMS), was synthesized to investigate the possibility of improving the stability of reagent-protein linkage chemistry. Radiolabeling of SPEMS with 211At generates succinimidyl N-2-(4-[211At]astatophenethyl)-N-methyl succinamate (Methyl-SAPS), with yields being consistent for greater than 1 year. Radiolabelings of 1 and SPEMS with 125I generated succinimidyl N-2-(4-[125I]iodophenethyl)succinamate (SIPS) and succinimidyl N-2-(4-[125I]iodophenethyl)-N-methyl succinamate (Methyl-SIPS), respectively, and showed no decline in yields. Methyl-SAPS, SAPS, Methyl-SIPS and SIPS were conjugated to Herceptin for a comparative assessment in LS-174T xenograft-bearing mice. The conjugates of Herceptin with Methyl-SAPS or Methyl-SIPS demonstrated immunoreactivity equivalent to if not superior to the SAPS and SIPS paired analogs. The in vivo studies also revealed that the N-methyl modification resulted in a superior statinated product.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Astatine,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Excipients,
http://linkedlifedata.com/resource/pubmed/chemical/Isotopes,
http://linkedlifedata.com/resource/pubmed/chemical/Radiopharmaceuticals
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| pubmed:status |
MEDLINE
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| pubmed:month |
May
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| pubmed:issn |
0969-8051
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
33
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
469-80
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| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16720238-Adenocarcinoma,
pubmed-meshheading:16720238-Animals,
pubmed-meshheading:16720238-Antibodies, Monoclonal,
pubmed-meshheading:16720238-Astatine,
pubmed-meshheading:16720238-Cell Line, Tumor,
pubmed-meshheading:16720238-Colonic Neoplasms,
pubmed-meshheading:16720238-Cross-Linking Reagents,
pubmed-meshheading:16720238-Drug Stability,
pubmed-meshheading:16720238-Excipients,
pubmed-meshheading:16720238-Humans,
pubmed-meshheading:16720238-Isotope Labeling,
pubmed-meshheading:16720238-Isotopes,
pubmed-meshheading:16720238-Metabolic Clearance Rate,
pubmed-meshheading:16720238-Mice,
pubmed-meshheading:16720238-Mice, Nude,
pubmed-meshheading:16720238-Organ Specificity,
pubmed-meshheading:16720238-Protein Binding,
pubmed-meshheading:16720238-Radiopharmaceuticals,
pubmed-meshheading:16720238-Tissue Distribution
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| pubmed:year |
2006
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| pubmed:articleTitle |
Preparation and in vivo evaluation of a novel stabilized linker for 211At labeling of protein.
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| pubmed:affiliation |
Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. vstalanov@msrce.howard.edu
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| pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Intramural
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