Turku PET Centre, University of Turku, FI-20521 Turku, Finland.
Turku Center for Disease Modeling, University of Turku, FI-20520 Turku, Finland.
Molecules. 2018 Jan 31;23(2):305. doi: 10.3390/molecules23020305.
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--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 [Ga]Ga or [F]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.
唾液酸结合免疫球蛋白样凝集素 9（Siglec-9）的 283-297 个氨基酸残基形成靶向血管黏附蛋白-1（VAP-1）的环状肽配体。VAP-1 与炎症时白细胞从血液向组织的转移有关。因此，Siglec-9 肽类似物是使用正电子发射断层扫描（PET）进行非侵入性炎症可视化的良好候选物。已经广泛评估了镓-68 标记的 1,4,7,10-四氮杂环十二烷-四乙酸（DOTA）缀合的 Siglec-9 用于此目的。在这里，我们探索了两种使用 1,4,7-三氮杂环壬烷-三乙酸（NOTA）螯合剂结合 [Ga]Ga 或 [F]AlF 标记 Siglec-9 肽的替代策略。通过体内 PET 成像和松节油诱导的无菌皮肤/肌肉炎症的 Sprague-Dawley 大鼠的离体γ计数评估了放射性配体。两种示踪剂都在发炎组织中清楚地积累。示踪剂的全身生物分布模式相似。
