Department of Nuclear Medicine, Fortis Memorial Research Institute, Gurgaon, India.
Cancer Biother Radiopharm. 2023 Sep;38(7):468-474. doi: 10.1089/cbr.2022.0080. Epub 2023 Apr 21.
Integrin αvβ6 has become an extremely promising theranostic target for precise delineation of fast-growing malignant cells in the recent years. The aim of the study was to validate the in-house kit-like synthesis of Ga-Trivehexin (integrin αvβ6) and to evaluate its uptake in patients with integrin αvβ6 expressing head and neck and pancreatic cancer. Ga-Trivehexin was synthesized by adding the variable amount of integrin αvβ6 (30-50 μg) to full volume (4-5 mL) Ga-68 in 0.05 M HCl and heating the reaction mixture at 90°C for 12 min at pH 3.5-4 to obtain the radiotracer with high radiochemical purity (RCP) and high yield. Quality control procedures were done to assess the RCP, stability, pyrogenicity and sterility of the radiotracer. Ga-Trivehexin was then administered in patients who met the eligibility criteria. Whole body PET/CT scans were done at variable time points post intravenous (i.v.) injection of 84-185 MBq of Ga-Trivehexin to assess its biodistribution and maximum uptake time. 0.2 mCi of Ga/μg of Trivehexin at 90°C for 12 min was the optimal parameter to obtain 85%-88% of noncorrected yield and 99% of RCP. The Ga-Trivehexin showed stability upto 6 h and was also found to be sterile and pyrogen free. Intense radiotracer uptake was noticed in the tumor and no uptake was noticed in healthy tissues. PET/CT imaging at 60 min post injection was found to be the optimal time for imaging the tumors with Ga-Trivehexin. The protocol for in-house kit-like labeling of Ga-Trivehexin was safe, reproducible, and cost-effective. Ga-Trivehexin is an extremely promising agent for noninvasive molecular imaging of integrin αvβ6 expressing tumors.
整合素 αvβ6 近年来已成为精确描绘快速生长的恶性细胞的极具前途的治疗诊断靶点。本研究旨在验证自主研发试剂盒样合成 Ga-三肽（整合素 αvβ6），并评估其在表达整合素 αvβ6 的头颈部和胰腺癌细胞患者中的摄取情况。Ga-三肽通过向全体积（4-5ml）Ga-68 中加入不同量的整合素 αvβ6（30-50μg），并在 pH3.5-4 下于 90°C 加热反应混合物 12 分钟，获得高放射化学纯度（RCP）和高产率的放射性示踪剂。进行质量控制程序以评估放射性示踪剂的 RCP、稳定性、致热性和无菌性。然后将 Ga-Trivehexin 施用于符合入选标准的患者。在静脉（i.v.）注射 84-185MBq Ga-Trivehexin 后的不同时间点进行全身 PET/CT 扫描，以评估其生物分布和最大摄取时间。在 90°C 下 0.2 mCi Ga/μg 三肽 12 分钟是获得 85%-88%非校正产率和 99%RCP 的最佳参数。Ga-Trivehexin 表现出 6 小时的稳定性，并且无菌且无热原。在肿瘤中观察到强烈的放射性示踪剂摄取，而在健康组织中未观察到摄取。注射后 60 分钟的 PET/CT 成像被发现是用 Ga-Trivehexin 对肿瘤进行成像的最佳时间。自主研发试剂盒样标记 Ga-Trivehexin 的方案安全、可重复且具有成本效益。Ga-Trivehexin 是一种非常有前途的用于表达整合素 αvβ6 的肿瘤的非侵入性分子成像剂。
