[68Ga] ga - dota - siglece -9在独立实验室中用于临床的替代自动合成方法的建立和验证

IF 4.4 Q1 CHEMISTRY, INORGANIC & NUCLEAR

EJNMMI Radiopharmacy and Chemistry Pub Date : 2025-10-20 DOI:10.1186/s41181-025-00396-x

Silvia Migliari, Alessandra Guercio, Anna Gagliardi, Roberta Giaccari, Stefano Bruno, Anne Roivainen, Sarita Forsback, Giorgio Baldari, Maura Scarlattei, Livia Ruffini

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引用次数: 0

摘要

Siglec-9是Siglec受体家族的一员，在调节免疫细胞运输和炎症中起着至关重要的作用，具有重要的临床意义。它主要在免疫细胞上表达，如中性粒细胞、单核细胞和树突状细胞——先天免疫和适应性免疫的关键组成部分。siglece -9与糖蛋白上的唾液酸残基结合，通常在内皮细胞上发现，这是炎症和组织损伤期间免疫调节的核心机制。值得注意的是，它与血管粘附蛋白1 (VAP-1)（一种内皮粘附分子）的相互作用对慢性炎症性疾病、自身免疫性疾病和癌症的治疗发展特别感兴趣。最近的研究表明，含有siglece -9基元的肽与1,4,7,10-四氮杂环十二烷-N， N ',N ',N ' -四乙酸（DOTA）结合，并用镓-68（[⁶⁸Ga]Ga-DOTA- siglece -9）进行放射性标记，可以有效地对这些病理状况进行正电子发射断层扫描（PET）成像。本研究旨在开发一种新的自动放射性标记方案，用于制备用于临床的[⁶⁸Ga]Ga- dota - siglece -9。合成过程采用全自动模块进行，实时监测关键参数，包括时间、温度和放射性。结果经标记条件优化和多肽稳定性评估，在65℃、6 min条件下，成功合成了[⁶⁸Ga]Ga- dota - siglece -9，放射化学收率（RY）为55.04%，放射化学纯度（RCP）为99.48%，摩尔活性（Am）为23.15 GBq/µmol。工艺验证得到一致的RY平均值（56.16%），RCP值（99.40%）。Am （20.26 GBq/µmol）。室温稳定性测试表明，[⁶⁸Ga]Ga- dota - siglece -9保持了可接受的RCP（平均99.29%）、pH、外观和无菌性。结论终产物符合Ph. Eur标准。质量要求，适合临床应用。

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Establishment and validation of an alternative automated synthesis of [68Ga]Ga-DOTA-Siglec-9 in an independent laboratory for clinical use

Background

Siglec-9, a member of the Siglec family of receptors, plays a crucial role in modulating immune cell trafficking and inflammation, with significant clinical implications. It is predominantly expressed on immune cells such as neutrophils, monocytes, and dendritic cells –key components of both innate and adaptive immunity. Siglec-9 binds to sialic acid residues on glycoproteins, commonly found on endothelial cells, a mechanism central to immune regulation during inflammation and tissue injury. Notably, its interaction with vascular adhesion protein 1 (VAP-1), an endothelial adhesion molecule, is of particular interest for therapeutic development in chronic inflammatory diseases, autoimmune disorders, and cancer. Recent studies have demonstrated that a Siglec-9 motif-containing peptide conjugated with 1,4,7,10-tetraazacyclododecane-N, N′,N′′,N′′′-tetraacetic acid (DOTA) and radiolabelled with gallium-68 ([⁶⁸Ga]Ga-DOTA-Siglec-9) enables effective positron emission tomography (PET) imaging of these pathological conditions. This study aimed to develop a new automated radiolabelling protocol for the preparation of [⁶⁸Ga]Ga-DOTA-Siglec-9 for clinical use. The synthesis was carried out using a fully automated module with real-time monitoring of key parameters including time, temperature, and radioactivity.

Results

Following optimization of labelling conditions and assessment of peptide stability, [⁶⁸Ga]Ga-DOTA-Siglec-9 was successfully synthesized with a radiochemical yield (RY) of 55.04%, radiochemical purity (RCP) of 99.48%, and molar activity (Am) of 23.15 GBq/µmol at 65 °C in 6 min. Process validation yielded consistent mean values of RY (56.16%), RCP (99.40%). and Am (20.26 GBq/µmol). Stability testing at room temperature over 3 h demonstrated that [⁶⁸Ga]Ga-DOTA-Siglec-9 maintained acceptable RCP (mean99.29%), pH, appearance, and sterility.