| In vitro cell studies of technetium-99m labeled RGD-HYNIC peptide, a comparison of tricine and EDDA as co-ligands. | |
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MedLine Citation:
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PMID: 12623113 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The level of alpha(V)beta(3) integrins on endothelial cells is elevated in angiogenesis. The high binding specificity to alpha(V)beta(3) integrins of peptides containing Arg-Gly-Asp (RGD) residues suggests that the radiolabeled RGD peptides may be useful as tumor specific imaging agents. In this research, cyclised peptides containing Arg-Gly-Asp (RGD) and Arg-Gly-Glu (RGE, as control) residues were conjugated with HYNIC and labeled with (99m)Tc. OBJECTIVE: The goal was to evaluate the influence of co-ligand, either tricine or ethylenediamine-N,N'-diacetic acid (EDDA) on protein and integrin binding and on cellular uptake in culture. METHODS: The n-octanol/water partition coefficient, binding to bovine serum albumin (BSA) and human umbilical vein endothelial (HUVE) cells, and cell lysate distributions of the radiolabeled peptides were evaluated. RESULTS: The co-ligands had a significant effect on the labeling efficiency of the HYNIC conjugates and on certain properties of the (99m)Tc complexes. The labeling efficiency with tricine was 10 fold higher and BSA binding was over 8 fold greater compared to EDDA. Both RGD labels showed higher (6 to 28 fold) binding to HUVE cells than that of the RGE labels, indicating binding specificity. After cell-lysis, only a small percentage of the total RGD label that accumulated in the cells was found bound to cellular proteins (9% of RGD/tricine and 5% of RGD/EDDA), implying that over 90% of the radiolabeled peptides were internalized for both radiolabeled RGDs. The number of the RGD molecules bound to proteins was estimated to be approximately three per cell, suggesting that only a small number of alpha(V)beta(3) integrin proteins are expressed on the cells. CONCLUSIONS: Apart from the differences in radiolabeling, the only important effect of substituting EDDA for tricine as co-ligand on the HYNIC-peptides was the lower degree of serum protein binding. In spite of the lower serum protein binding potential, in vivo tumor accumulation of the RGD/EDDA may not be improved compared to RGD/tricine since quantitation of the cell binding results suggests that the number of alpha(V)beta(3) integrin proteins per cell might be limited. |
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Authors:
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Zi-Fen Su; Jiang He; Mary Rusckowski; Donald J Hnatowich |
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Publication Detail:
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Type: Comparative Study; Evaluation Studies; Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Nuclear medicine and biology Volume: 30 ISSN: 0969-8051 ISO Abbreviation: Nucl. Med. Biol. Publication Date: 2003 Feb |
Date Detail:
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Created Date: 2003-03-07 Completed Date: 2003-10-27 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9304420 Medline TA: Nucl Med Biol Country: England |
Other Details:
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Languages: eng Pagination: 141-9 Citation Subset: IM |
Affiliation:
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Division of Nuclear Medicine, Department of Radiology, University of Massachusetts Medical School, Worcester, MA 01655, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Blood Proteins
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metabolism* Cells, Cultured Edetic Acid / analogs & derivatives*, diagnostic use, pharmacokinetics Endothelium, Vascular / metabolism*, radionuclide imaging Glycine / analogs & derivatives*, diagnostic use, pharmacokinetics Humans Hydrazines / diagnostic use, pharmacokinetics* Integrins / metabolism* Ligands Metabolic Clearance Rate Nicotinic Acids / diagnostic use, pharmacokinetics* Oligopeptides / diagnostic use, pharmacokinetics* Protein Binding Radiopharmaceuticals / chemical synthesis, diagnostic use, pharmacokinetics Technetium / diagnostic use, pharmacokinetics* Umbilical Veins / metabolism, radionuclide imaging |
| Chemical | |
Reg. No./Substance:
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0/6-hydrazinopyridine-3-carboxylic acid; 0/Blood Proteins; 0/Hydrazines; 0/Integrins; 0/Ligands; 0/Nicotinic Acids; 0/Oligopeptides; 0/Radiopharmaceuticals; 56-40-6/Glycine; 5657-17-0/EDDA; 5704-04-1/tricine; 60-00-4/Edetic Acid; 7440-26-8/Technetium; 99896-85-2/arginyl-glycyl-aspartic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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