By a News Reporter-Staff News Editor at Life Science Weekly -- Data detailed on Molecular Imaging have been presented. According to news reporting from Uppsala, Sweden, by NewsRx journalists, research stated, "Affibody molecules are a class of affinity agents for molecular imaging based on a non-immunoglobulin protein scaffold. Previous studies have demonstrated high contrast for in vivo imaging of cancer-associated molecular abnormalities using Affibody molecules."
The news correspondents obtained a quote from the research from Uppsala University, "Using the radionuclide F-18 for labeling and PET as the imaging modality, the sensitivity of molecular imaging using Affibody molecules can be further increased. The use of oxime formation between an aminooxy-functionalized peptide and F-18-fluorobenzaldehyde (F-18-FBA) is a promising way of radiolabeling of targeting peptides. However, previous studies demonstrated that application of this method to Affibody molecules is associated with high liver uptake. We hypothesized that incorporation of a triglutamyl spacer between the aminooxy moiety and the N-terminus of a synthetic Affibody molecule would decrease the hepatic uptake of the F-18-N-(4-fluorobenzylidine)oxime) (F-18-FBO)-labeled tracer. To verify this, we have produced two variants of the HER2-targeting Z(HER2:342) Affibody molecule by peptide synthesis: OA-PEP4313, where aminooxyacetic acid was conjugated directly to the N-terminal alanine, and OA-E-3-PEP4313, where a triglutamyl spacer was introduced between the aminooxy moiety and the N-terminus. We have found that the use of the spacer is associated with a minor decrease of affinity, from K-D = 49 pM to K-D = 180 pM. Radiolabeled F-18-FBO-E-3-PEP4313 demonstrated specific binding to HER2-expressing ovarian carcinoma SKOV-3 cells and slow internalization. Biodistribution studies in mice demonstrated that the use of a triglutamyl linker decreased uptake of radioactivity in liver 2.7-fold at 2 h after injection. Interestingly, radioactivity uptake in kidneys was also reduced (2.4-fold). Experiments in BALB/C nu/nu mice bearing SKOV-3 xenografts demonstrated HER2-specific uptake of F-18-FBO-E-3-PEP4313 in tumors. At 2 h pi, the tumor uptake (20 +/- 2% ID/g) exceeded uptake in liver 5-fold and uptake in kidneys 3.6-fold. The tumor-to-blood ratio was 21 +/- 3. The microPET/CT imaging experiment confirmed the biodistribution data."
According to the news reporters, the research concluded: "The use of a triglutamyl spacer is a convenient way to improve the biodistribution profile of Affibody molecules labeled at the N-terminus using F-18-FBA. It provides a tracer capable of producing high-contrast images of HER2-expressing tumors."
For more information on this research see: Incorporation of a Triglutamyl Spacer Improves the Biodistribution of Synthetic Affibody Molecules Radiofluorinated at the N-Terminus via Oxime Formation with F-18-4-Fluorobenzaldehyde. Bioconjugate Chemistry, 2014;25(1):82-92. Bioconjugate Chemistry can be contacted at: Amer Chemical Soc, 1155 16TH St, NW, Washington, DC 20036, USA. (American Chemical Society - www.acs.org; Bioconjugate Chemistry - www.pubs.acs.org/journal/bcches)
Our news journalists report that additional information may be obtained by contacting D. Rosik, Uppsala University, Rudbeck Lab, Unit Biomed Radiat Sci, Uppsala, Sweden. Additional authors for this research include A. Thibblin, G. Antoni, H. Honarvar, J. Strand, R.K. Selvaraju, M. Altai, A. Orlova, A.E. Karlstrom and V. Tolmachev (see also Molecular Imaging).
Keywords for this news article include: Sweden, Europe, Uppsala, Nanotechnology, Molecular Imaging, Emerging Technologies
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