非金属螯合剂法制备靶向PSMA分子探针18F-PSMA-1007及其初步临床意义的探究

Preparation of the targeted PSMA molecular probe 18F-PSMA-1007 using a non-metallic chelator method and exploration of its preliminary clinical application

    摘要
  • 摘要:
    目的  制备靶向前列腺特异性膜抗原（PSMA）的分子探针18F-PSMA-1007，并对该分子探针的临床应用进行初步研究。
    方法 采用亲核取代反应制备18F-PSMA-1007，经PS-H+柱中和溶液后，通过C18ec柱捕获，先用梯度浓度的乙醇（5%~30%）进行纯化，最后用抗坏血酸钠和磷酸盐缓冲液稀释，经0.22 μm 微孔无菌滤膜过滤，得到最终纯化产品，测定其放射化学纯度和体外稳定性。临床试验纳入2024年6月至2024年12月在昆明医科大学第三附属医院云南省肿瘤医院接受18F-PSMA-1007 PET/CT检查的5名男性健康受试者年龄（60.5±5.1）岁和1例前列腺癌（PCa）患者（男性，65岁）进行前瞻性队列研究。测量18F-PSMA-1007在脑、泪腺、腮腺、下颌下腺、甲状腺、心脏、肺、肝脏、胆囊、胰腺、脾脏、肾脏、红骨髓、骨原细胞、胃、肠及肌肉等组织器官的放射性浓度，计算各组织或器官的内照射吸收剂量及全身有效剂量。
    结果 18F-PSMA-1007注射液未衰变校正的放射性化学产率为（60.0±3.5）%，放射化学纯度>95%，比活度为18.2~20.1（16.4±4.4） MBq/nmol ，在体外具备良好的稳定性。在健康志愿者体内，18F-PSMA-1007主要分布在肝脏、肾脏、肠、泪腺、腮腺和下颌下腺等部位，其中肝脏的内照射吸收剂量最高（165.84±26.78） μGy/MBq，而骨原细胞中较低（12.35±2.35） μGy/MBq；健康受试者的全身有效剂量为（0.0145±0.0015） mSv/MBq。PCa患者的18F-PSMA-1007 PET/CT显像显示多发骨转移病灶。
    结论 采用亲核取代反应制备的PSMA分子探针18F-PSMA-1007在PCa的诊断方面具有重要临床意义。

     

    Abstract:
    Objective Preparation of the molecular probe 18F-prostate specific membrane antigen (PSMA)-1007 targeting PSMA and preliminary investigation of its clinical application.
    Methods The 18F-PSMA-1007 was prepared via nucleophilic substitution reaction, neutralized over a PS-H+column, the product was captured by a C18ec column, and initially purified using gradient concentrations of ethanol (5%−30%), and subsequently diluted with a mixture of sodium ascorbate and sodium phosphate buffer, filtered through a 0.22 µm sterile microporous membrane to obtain the final purified product. Its radiochemical purity and in vitro stability were determined. A prospective cohort study was conducted involving 5 male healthy volunteers (aged (60.5±5.1) years) and 1 prostate cancer (PCa) patient (male, 65 years old) who underwent 18F-PSMA-1007 PET/CT examinations in the Third Affiliated Hospital of Kunming Medical University, Yunnan Cancer Hospital from June 2024 to December 2024. Radioactive concentration of 18F-PSMA-1007 was measured in various tissues and organs, including the brain, lacrimal gland, parotid gland, submandibular gland, thyroid gland, heart, lung, liver, gallbladder, pancrea, spleen, kidney, red bone marrow, bone progenitor cell, stomach, intestine, and muscle. Subsequently, the internal exposure absorbed dose of each tissue and organ and the whole-body effective dose were calculated.
    Results The radiochemical yield without decay correction of 18F-PSMA-1007 injection was (60.0±3.5)%, with a radiochemical purity of >95%, and the specific activity was 18.2−20.1 (16.4±4.4) MBq/nmol, which indicated good stability in vitro, 18F-PSMA-1007 was primarily distributed in the liver, kidney, intestine, lacrimal gland, parotid gland, and submandibular gland. The liver showed the highest internal absorbed radiation dose ((165.84±26.78) µGy/MBq), and that in the bone progenitor cell was lower ((12.35±2.35) µGy/MBq). The whole-body effective dose of healthy volunteers was (0.014 5±0.001 5) mSv/MBq. Multiple bone metastases lesions can be observed in the 18F-PSMA-1007 PET/CT imaging of PCa patients.
    Conclusions The 18F-PSMA-1007 molecular probe prepared via nucleophilic substitution reaction holds significant clinical importance for the diagnosis of PCa.

     

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