Fluorine-18 Labeling of S100 Proteins for Small Animal Positron Emission Tomography

  • Markus Laube
  • Torsten Kniess
  • Christin Neuber
  • Cathleen Haase-Kohn
  • Jens PietzschEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1929)


The interaction of S100 proteins (S100s), a multigenic family of Ca2+-binding and Ca2+-modulated proteins, with pattern recognition receptors, e.g., Toll-like receptors (TLRs), the receptor for advanced glycation end products (RAGE), or scavenger receptors (SR), is hypothesized to be of high relevance in the pathogenesis of various diseases. This includes chronic inflammatory conditions, atherosclerosis, cardiomyopathies, neurodegeneration, and progression of cancers. However, data concerning the role of circulating S100s in these pathologies are scarce. One reason for this is the shortage of suitable radiolabeling methods for direct assessment of the metabolic fate of circulating S100s in vivo. We report a radiotracer approach using radiolabeling of recombinant human S100s with the positron emitter fluorine-18 (18F) by conjugation with N-succinimidyl 4-[18F]fluorobenzoate ([18F]SFB). The methodological radiochemical part focuses on an optimized and automated synthesis of [18F]SFB comprising HPLC purification to achieve higher chemical purity. The respective radioligands, [18F]fluorobenzoylated S100s ([18F]FB-S100s), were obtained with appropriate radiochemical purities, yields, and effective molar activities. Biological applications comprise cell and tissue binding experiments in vitro, biodistribution and metabolite studies in rodents in vivo/ex vivo, and dynamic positron emission tomography studies using dedicated small animal PET systems. Radiolabeling of S100s with 18F and, particularly, the use of small animal PET provide novel probes to delineate both their metabolic fate and the functional expression of their specific receptors under normal and pathophysiological conditions in rodent models of disease.

Key words

Bolton-Hunter-type reagent In vivo imaging Radiopharmacological characterization 18F-building block Module-assisted radiosynthesis S100 proteins Calcium EF hand 



We apologize to those researchers whose works have not been mentioned due to space restrictions. We are especially grateful to our former colleagues Susan Hoppmann, Ph.D.; Susann Wolf, Ph.D.; and Nadine Herwig (née Tandler), Ph.D., who all received their doctorate in the field of S100 protein research at the Technische Universität Dresden, Faculty of Chemistry and Food Chemistry, Germany, and also to Christoph Tondera, Ph.D., for the dedicated work and many stimulating and fruitful discussions. The authors thank the staff of the cyclotron and GMP radiopharmaceuticals production units for providing [18F]fluoride. The expert technical assistance of Mareike Barth, Catharina Heinig, Regina Herrlich, Uta Lenkeit, Sebastian Meister, Aline Morgenegg, and Andrea Suhr also is greatly acknowledged. Jens Pietzsch is thankful to the Deutsche Forschungsgemeinschaft (DFG) for supporting this work by research grant PI 304/1-1 “Bildgebende In-vivo-Charakterisierung von Rezeptoren für Advanced Glycation End products mittels Kleintier-Positronen-Emissions-Tomographie” and within the Collaborative Research Center Transregio 67 “Functional Biomaterials for Controlling Healing Processes in Bone und Skin—From Material Science to Clinical Application” (CRC/TRR 67/3). This work also is part of the intramural research initiative “Radiation-Induced Vascular Dysfunction (RIVAD).”


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Markus Laube
    • 1
  • Torsten Kniess
    • 2
  • Christin Neuber
    • 1
  • Cathleen Haase-Kohn
    • 1
  • Jens Pietzsch
    • 1
    • 3
    Email author
  1. 1.Department of Radiopharmaceutical and Chemical BiologyHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer ResearchDresdenGermany
  2. 2.Department of GMP Radiopharmaceuticals ProductionHelmholtz-Zentrum Dresden-Rossendorf, Institute of Radiopharmaceutical Cancer ResearchDresdenGermany
  3. 3.Faculty of Chemistry and Food ChemistryTechnische Universität DresdenDresdenGermany

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