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New Xenografts Study Results Reported from University of California (Development of a Radio labeled Irreversible Peptide Ligand for PET Imaging of...

July 4, 2014



New Xenografts Study Results Reported from University of California (Development of a Radio labeled Irreversible Peptide Ligand for PET Imaging of Vascular Endothelial Growth Factor)

By a News Reporter-Staff News Editor at Angiogenesis Weekly -- Fresh data on Biotechnology are presented in a new report. According to news reporting from Davis, California, by NewsRx journalists, research stated, "Imaging agents based on peptide probes have desirable pharmacokinetic properties provided that they have high affinities for their target in vivo. An approach to improve a peptide ligand's affinity for its target is to make this interaction covalent and irreversible."

The news correspondents obtained a quote from the research from the University of California, "For this purpose, we evaluated a Cu-64-labeled affinity peptide tag, Cu-64-L19K-(5-fluoro-2,4-dinitrobenzene) (Cu-64-L19K-FDNB), which binds covalently and irreversibly to vascular endothelial growth factor (VEGF) as a PET imaging agent. We compared the in vivo properties of Cu-64-L19K-FDNB in VEGF-expressing tumor xenografts with its noncovalent binding analogs, Cu-64-L19K-(2,4-dinitrophenyl) (Cu-64-L19K-DNP) and Cu-64-L19K. The L19K peptide (GGNECDIARMWEWECFERK-CONH2) was constructed with 1,4,7-triazacyclononane-1,4,7-triacetic acid at the N terminus for radiolabeling with Cu-64 with a polyethylene glycol spacer between peptide and chelate. 1,5-difluoro-2,4-dinitrobenzene was conjugated at the C-terminal lysine for cross-linking to VEGF, resulting in L19K-FDNB. Cu-64-L19K-FDNB was assayed for covalent binding to VEGF in vitro. As a control, L19K was conjugated to 1-fluoro-2,4-dinitrobenzene, resulting in L19K-DNP. PET imaging and biodistribution studies of Cu-64-L19K-FDNB, Cu-64-L19K-DNP, and the native Cu-64-L19K were compared in HCT-116 xenografts. Blocking studies of Cu-64-L19K-FDNB was performed with a coinjection of excess unlabeled L19K-FDNB. In vitro binding studies confirmed the covalent and irreversible binding of Cu-64-L19K-FDNB to VEGF, whereas Cu-64-L19K-DNP and Cu-64-L19K did not bind covalently. PET imaging showed higher tumor uptake with Cu-64-L19K-FDNB than with Cu-64-L19K-DNP and Cu-64-L19K, with mean standardized uptake values of 0.62 +/- 0.05, 0.18 +/- 0.06, and 0.34 +/- 0.14, respectively, at 24 h after injection (P < 0.05), and 0.53 +/- 0.05, 0.32 +/- 0.14, and 0.30 +/- 0.09, respectively, at 48 h after injection (P < 0.05). Blocking studies with Cu-64-L19K-FDNB in the presence of excess unlabeled peptide showed a 53% reduction in tumor uptake at 48 h after injection. In this proof-of-concept study, the use of a covalent binding peptide ligand against VEGF improves tracer accumulation at the tumor site in vivo, compared with its noncovalent binding peptide analogs."

According to the news reporters, the research concluded: "This technique is a promising tool to enhance the potency of peptide probes as imaging agents."

For more information on this research see: Development of a Radio labeled Irreversible Peptide Ligand for PET Imaging of Vascular Endothelial Growth Factor. Journal of Nuclear Medicine, 2014;55(6):1029-1034. Journal of Nuclear Medicine can be contacted at: Soc Nuclear Medicine Inc, 1850 Samuel Morse Dr, Reston, VA 20190-5316, USA (see also Biotechnology).

Our news journalists report that additional information may be obtained by contacting B.V. Marquez, University of California, Dept. of Chem, Davis, CA 95616, United States. Additional authors for this research include O.F. Ikotun, J.J. Parry, B.E. Rogers, C.F. Meares and S.E. Lapi.

Keywords for this news article include: VEGF, Biotechnology, Davis, Xenograft, California, United States, Protein Kinases, Membrane Proteins, Xenotransplantion, Angiogenic Proteins, Phosphotransferases, Growth Factor Receptors, North and Central America, Receptor Protein-Tyrosine Kinases, Vascular Endothelial Growth Factors

Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC


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Source: Angiogenesis Weekly


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