Exploring Alternative Radiolabeling Strategies for Sialic Acid-Binding Immunoglobulin-Like Lectin 9 Peptide: [68Ga]Ga- and [18F]AlF-NOTA-Siglec-9

Molecules. 2018 Jan 31;23(2):305. doi: 10.3390/molecules23020305.

Abstract

Amino acid residues 283-297 from sialic acid-binding immunoglobulin-like lectin 9 (Siglec-9) form a cyclic peptide ligand targeting vascular adhesion protein-1 (VAP-1). VAP-1 is associated with the transfer of leukocytes from blood to tissues upon inflammation. Therefore, analogs of Siglec-9 peptide are good candidates for visualizing inflammation non-invasively using positron emission tomography (PET). Gallium-68-labeled 1,4,7,10-tetraazacyclododecane-N,N',N″,N‴-tetraacetic acid (DOTA)-conjugated Siglec-9 has been evaluated extensively for this purpose. Here, we explored two alternative strategies for radiolabeling Siglec-9 peptide using a 1,4,7-triazacyclononane-triacetic acid (NOTA)-chelator to bind [68Ga]Ga or [18F]AlF. The radioligands were evaluated by in vivo PET imaging and ex vivo γ-counting of turpentine-induced sterile skin/muscle inflammation in Sprague-Dawley rats. Both tracers showed clear accumulation in the inflamed tissues. The whole-body biodistribution patterns of the tracers were similar.

Keywords: Siglec-9; VAP-1; aluminum fluoride; fluorine-18; gallium-68; inflammation; positron emission tomography.

MeSH terms

  • Animals
  • Antigens, CD* / chemistry
  • Antigens, CD* / pharmacology
  • Fluorine Radioisotopes*
  • Gallium Isotopes*
  • Heterocyclic Compounds* / chemistry
  • Heterocyclic Compounds* / pharmacology
  • Heterocyclic Compounds, 1-Ring
  • Isotope Labeling / methods*
  • Positron-Emission Tomography / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Sialic Acid Binding Immunoglobulin-like Lectins* / chemistry
  • Sialic Acid Binding Immunoglobulin-like Lectins* / pharmacology

Substances

  • Antigens, CD
  • Fluorine Radioisotopes
  • Gallium Isotopes
  • Heterocyclic Compounds
  • Heterocyclic Compounds, 1-Ring
  • SIGLEC9 protein, human
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • 1,4,7-triazacyclononane-N,N',N''-triacetic acid
  • Fluorine-18