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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-4-28
pubmed:abstractText
Cyclic arginine-glycine-aspartate (RGD) peptides and their derivatives have been intensively studied as tumor targeting probes. One major drawback, however, is their short blood circulation half-lives, which greatly compromises their targeting efficacy. To address this issue, a cyclic peptide, c(RGDyK), and an organic dye (IRDye800 or Cy5.5) were covalently conjugated onto human serum albumin (HSA). The conjugates were subjected to in vitro cell staining, in vivo near-infrared fluorescence (NIRF) imaging, ex vivo NIRF imaging, and histologic studies to evaluate their feasibility as tumor imaging probes. As a control, RAD peptide was also coupled with HSA and labeled with IRDye800 for in vivo imaging. The HSA-RGD-IRDye800 exhibited integrin alpha(v)beta(3)-specific binding in cell staining experiment. In vivo NIRF imaging showed higher tumor accumulation and tumor to background contrast of HSA-RGD-IRDye800 over RGD-IRDye800. The integrin specificity of HSA-RGD-IRDye800 is confirmed by both successful inhibition of tumor uptake in the presence of c(RGDyK) and the inability to accumulate in integrin-positive tumors by RAD-HSA-IRDye800. Histologic examination revealed initial tumor vascular binding and eventually both tumor vasculature and tumor cell integrin binding in vivo. In summary, we successfully developed an RGD-based protein conjugate with prolonged circulation half-life for NIRF imaging of tumor integrin alpha(v)beta(3) expression. The success of this study may be generalizable for other peptide-based probes to be conjugated with HSA for prolonged tumor contrast and improved pharmacokinetics.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1535-3508
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
65-73
pubmed:dateRevised
2011-4-7
pubmed:meshHeading
pubmed-meshheading:19397852-Animals, pubmed-meshheading:19397852-Carbocyanines, pubmed-meshheading:19397852-Cell Line, Tumor, pubmed-meshheading:19397852-Disease Models, Animal, pubmed-meshheading:19397852-Half-Life, pubmed-meshheading:19397852-Histocytochemistry, pubmed-meshheading:19397852-Humans, pubmed-meshheading:19397852-Indoles, pubmed-meshheading:19397852-Integrin alphaVbeta3, pubmed-meshheading:19397852-Mice, pubmed-meshheading:19397852-Mice, Nude, pubmed-meshheading:19397852-Molecular Probe Techniques, pubmed-meshheading:19397852-Neoplasm Transplantation, pubmed-meshheading:19397852-Neoplasms, Experimental, pubmed-meshheading:19397852-Peptides, Cyclic, pubmed-meshheading:19397852-Protein Binding, pubmed-meshheading:19397852-Serum Albumin, pubmed-meshheading:19397852-Spectroscopy, Near-Infrared, pubmed-meshheading:19397852-Tissue Distribution
pubmed:articleTitle
RGD-human serum albumin conjugates as efficient tumor targeting probes.
pubmed:affiliation
Molecular Imaging Program at Stanford, Department of Radiology and Bio-X Program, Stanford University School of Medicine, Standford, CA 94305-5484, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural