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Amino Acids

, Volume 41, Issue 4, pp 809–820 | Cite as

Expression, purification and fluorine-18 radiolabeling of recombinant S100A4: a potential probe for molecular imaging of receptor for advanced glycation endproducts in vivo?

  • Susann Wolf
  • Cathleen Haase-Kohn
  • Jens Lenk
  • Susan Hoppmann
  • Ralf Bergmann
  • Joerg Steinbach
  • Jens PietzschEmail author
Original Article

Abstract

Data concerning the pathophysiological role of extracellular S100A4, a member of the multigenic family of Ca2+-modulated S100 proteins, and its interaction with the receptor for advanced glycation endproducts (RAGE) or other putative receptors in tumorigenesis, metastasis, and inflammatory processes in vivo are scarce. One reason is the shortage of suitable radiotracer methods. We report a novel methodology using recombinant human S100A4 as potential probe for molecular imaging and functional characterization of this interaction. Therefore, human S100A4 was cloned as GST fusion protein in the bacterial expression vector pGEX-6P-1 and expressed in E. coli strain BL21. Purified recombinant human S100A4 was radiolabeled with the positron emitter fluorine-18 (18F) by conjugation with N-succinimidyl-4-[18F]fluorobenzoate ([18F]SFB). The radioligand [18F]fluorobenzoyl-S100A4 (18F-S100A4) was used in cell binding experiments in RAGE-bearing human melanoma cells and endothelial cells in vitro, and in both biodistribution experiments and small animal positron emission tomography (PET) studies in normal rats in vivo. The cellular association and tissue-specific distribution of 18F-S100A4 in vitro and in vivo correlated well with the protein expression and anatomical localization of RAGE, e.g., in the vascular system and in lung. Compared to other S100 RAGE radioligands, the overall findings of this study indicate that extracellular S100A4 in vivo shows only a moderate interaction with RAGE and, furthermore, exhibits a substantially faster metabolic degradation. On the other hand, the approach allows the use of quantitative small animal PET and provides a novel probe to both delineate functional expression and differentiate multiligand interaction of RAGE under normal and pathophysiological conditions in rodent models of disease.

Keywords

Endothelial cells Melanoma cells Molecular imaging Multiligand receptors Protein radiolabeling Small animal positron emission tomography (PET) S100 proteins 

Notes

Acknowledgments

The authors are grateful to Mareike Barth, Catharina Heinig, Regina Herrlich, Uta Lenkeit, and Aline Morgenegg for their expert technical assistance. The authors thank Torsten Kniess, Ph.D., and Birgit Mosch, Ph.D. for their expert advice and many stimulating discussions. This work in part was supported by a grant from the Deutsche Forschungsgemeinschaft (DFG; grant no. PI304/1-1).

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Susann Wolf
    • 1
  • Cathleen Haase-Kohn
    • 1
  • Jens Lenk
    • 1
  • Susan Hoppmann
    • 1
    • 2
  • Ralf Bergmann
    • 1
  • Joerg Steinbach
    • 1
  • Jens Pietzsch
    • 1
    Email author
  1. 1.Department of Radiopharmaceutical BiologyInstitute of Radiopharmacy, Research Center Dresden-RossendorfDresdenGermany
  2. 2.Molecular Imaging Program at Stanford (MIPS), Department of RadiologyStanford UniversityStanfordUSA

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