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

Olli Moisio,Riikka Siitonen,Xiang-Guo Li,Elli Suomela,Heidi Liljenbäck,Anne Roivainen,Sirpa Jalkanen

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.

Highlights

Inflammation is associated with several diseases including atherosclerosis, rheumatoid arthritis, and certain cancers
Glucose uptake in regions of inflammation is higher than normal, [18 F]FDG is not a specific tracer for inflammation, which can lead to false positives
The two radiolabeling methods described here are good alternatives for producing Siglec-9 peptide-based Positron emission tomography (PET) tracers for imaging of inflammation

Summary

Introduction

Inflammation is associated with several diseases including atherosclerosis, rheumatoid arthritis, and certain cancers. Positron emission tomography (PET) imaging offers a valuable diagnostic and research tool for in vivo detection and quantification of inflammation in a non-invasive manner [1,2]. The most commonly used PET-radiotracer, 2-deoxy-2-[18 F]-fluoro-D-glucose ([18 F]FDG), has been employed for many indications involving inflammation [3], including the assessment of atherosclerotic plaques [4]. Development of alternative, inflammation-specific PET radiotracers is justified. Potential alternative targets for PET imaging of inflammatory conditions include somatostatin receptors [5,6,7], 18 kDa translocator protein [8], B-lymphocyte antigen CD20 [9], and, more recently, CXCR4 chemokine receptors [10,11,12]

Methods

Results

Conclusion