摘要
^(68)Ga-DOTA-TATE已成功应用于临床神经内分泌肿瘤的诊断,但^(68)Ga半衰期短,应用受到限制。为开展[^(18)F]AlF-NOTA-TATE的制备及临床验证,以满足神经内分泌肿瘤(NETs)患者的诊断、疗效评估等临床需求,本研究开发了一种新的柱色层纯化[^(18)F]AlF-NOTA-TATE方法,并在临床型单管多功能氟合成模块上自动化合成。同时研究[^(18)F]AlF-NOTA-TATE的脂水分配系数、体外稳定性和药代动力学,在荷NCI-H69(SSTR2阳性表达)小细胞肺癌裸鼠上行生物分布实验及PET/CT显像,并对3例NETs患者进行初步临床应用。结果表明,新的柱色层纯化[^(18)F]AlF-NOTA-TATE方法简单、合成时间短、放化纯度大于95%,乙醇含量低于3%。BALB/c小鼠药代动力学及荷瘤鼠生物分布实验结果表明,药物血液清除较快,主要通过肾脏代谢。荷瘤鼠PET/CT显像显示,SSTR阳性肿瘤特异性摄取放射性药物;初步临床应用显示,[^(18)F]AlF-NOTA-TATE在患者体内靶向性好,滞留时间较长,图像质量较好。以上结果表明,柱色层法纯化[^(18)F]AlF-NOTA-TATE方法简单、放化纯度高,初步临床表明[^(18)F]AlF-NOTA-TATE有进一步临床研究的价值。
^(68)Ga-DOTA-TATE has been successfully applied in the diagnosis of clinical neuroendocrine tumors,but its short half-life limits its widespread use.This study aimed to develop[^(18)F]AlF-NOTA-TATE to meet the clinical demands of patients with neuroendocrine tumors(NETs)for diagnosis and treatment evaluation.A new column chromatography purification method for[^(18)F]AlF-NOTA-TATE was developed and automated synthesis was performed using a clinical single-vessel multi-functional fluorine synthesis module.The lipophilicity,in vitro stability,and pharmacokinetics of[^(18)F]AlF-NOTA-TATE were studied,and biodistribution experiments and PET/CT imaging of nude mice with NCI-H69(SSTR2 positive expression)small cell lung cancer were conducted,followed by preliminary clinical evaluation on three patients with neuroendocrine tumors.The new column chromatography purification method for[^(18)F]AlF-NOTA-TATE was simple,which was synthesized in a short time with higher than 95%of radiochemical purity and,less than 3%of.ethanol content.Pharmacokinetic and biodistribution experiments in BALB/c mice showed rapid blood clearance of the drug and renal metabolism.PET/CT imaging of tumor-bearing mice showed specific uptake of the radiotracer in SSTR-positive tumors.Preliminary clinical application showed that[^(18)F]AlF-NOTA-TATE is well targeted in patients with long retention time and can provide better image quality.The column chromatography method for the preparation of[^(18)F]AlF-NOTA-TATE was simple and had high radiochemical purity.Preliminary clinical results suggested that[^(18)F]AlF-NOTA-TATE has further value for clinical research.
作者
刘欢欢
张晓军
麻广宇
张锦明
LIU Huanhuan;ZHANG Xiaojun;MA Guangyu;ZHANG Jinming(Department of Nuclear Medicine,the First Medical Center,Chinese PLA General Hospital,Beijing 100853,China;Medical School of Chinese PLA,Beijing 100853,China)
出处
《同位素》
CAS
2024年第4期379-386,共8页
Journal of Isotopes
基金
国家同位素工程技术研究中心开放课题资助项目(GJTESGCZX-202307)。
