Linked Life Data

16417253

Source:http://linkedlifedata.com/resource/pubmed/id/16417253

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-18
pubmed:abstractText
Diabodies are single chain antibody fragments (scFvs) that spontaneously form bivalent dimers of molecular size 50-55000. Radiolabeled diabodies are almost ideal tumor targeting agents due to their high avidity (bivalent) binding to tumor antigens and small size (50-55000) that leads to improved tumor-to-blood ratio compared to intact antibodies (150000). However, due to their high retention and metabolism in the kidney, radioiodine is the current radiolabel of choice for diabodies since radioiodine is rapidly excreted from the kidney once metabolized. We have previously shown that 111In-DOTA-diabody gives higher tumor uptake in nude mouse xenografts than 125I-diabody, but has extremely high kidney retention since its 111In-labeled metabolites are retained by and only slowly excreted from the kidney. When a diabody is conjugated to a bifunctional PEG-3400 derivative followed by reaction with cysteinyl-DOTA, the resulting product has an apparent molecular size of 75000 and a Stokes radius of 35 angstroms on size exclusion chromatography, compared to a Stokes radius of 25 angstroms for intact diabody. When radiolabeled, the conjugate gives high yields of 111In-labeled product, retains high immunoreactivity, and gives improved biodistributions (30-40%ID/g, 12-48 h) compared to 111In-DOTA-diabody (12-13%ID/g, 6-12 h). We show that the improved biodistribution is due to an increase in Stokes radius caused by the linear PEG-3400 since conjugation of diabody with multiple (PEG)12 linkers followed by reaction with cysteinyl-DOTA does not reduce kidney accumulation. We also show that 111In-cysteinyl-DOTA-PEG3400-diabody gives excellent tumor images in the nude mouse xenograft model and that 125I-PEG3400-diabody gives equivalent images to 125I-minibody (molecular size, 80000), but improved tumor-to-liver ratios, suggesting that this imaging agent can be used to image liver metastases.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1043-1802
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
68-76
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:16417253-Animals, pubmed-meshheading:16417253-Carcinoembryonic Antigen, pubmed-meshheading:16417253-Cell Line, Tumor, pubmed-meshheading:16417253-Chelating Agents, pubmed-meshheading:16417253-Cysteine, pubmed-meshheading:16417253-Female, pubmed-meshheading:16417253-Heterocyclic Compounds, 1-Ring, pubmed-meshheading:16417253-Immunoglobulin Fragments, pubmed-meshheading:16417253-Indium Radioisotopes, pubmed-meshheading:16417253-Kidney, pubmed-meshheading:16417253-Mice, pubmed-meshheading:16417253-Mice, Nude, pubmed-meshheading:16417253-Neoplasm Transplantation, pubmed-meshheading:16417253-Neoplasms, pubmed-meshheading:16417253-Polyethylene Glycols, pubmed-meshheading:16417253-Radioimmunodetection, pubmed-meshheading:16417253-Radiopharmaceuticals, pubmed-meshheading:16417253-Tissue Distribution
pubmed:articleTitle
Improved biodistribution and radioimmunoimaging with poly(ethylene glycol)-DOTA-conjugated anti-CEA diabody.
pubmed:affiliation
Division of Immunology, Beckman Research Institute of the City of Hope, Duarte, California 91010, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural