Department of Nuclear Medicine, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, Sichuan 646000, China.
Contrast Media Mol Imaging. 2022 Feb 25;2022:7684076. doi: 10.1155/2022/7684076. eCollection 2022.
Bone is a common site of metastasis from a malignant tumor. Several radiopharmaceuticals are available to relieve bone pain in patients with cancer. However, every radiopharmaceutical has its own disadvantages, and there is still a need to investigate easily accessible and high bone affinity radiopharmaceuticals. Ibandronate (IBA) and Re were used for radiolabeling to develop and evaluate a novel type of bone-seeking radiopharmaceutical.
The preparation conditions of [Re]Re-IBA were investigated, and thin-layer chromatography was used to analyze radiochemical purity. The stability, plasma protein binding rate, lipid-water distribution coefficient, safety and biodistribution in normal mice, and bone imaging of [Re]Re-IBA in New Zealand rabbits were studied. In addition, the nude mice model of bone metastasis was established, and biodistribution and imaging characteristics of [Re]Re-IBA in these nude mice were studied.
[Re]Re-IBA was successfully prepared with radiochemical purity >95%. The optimum preparation conditions were as follows: IBA, 0.8-1.4 mg; ascorbic acid, 0.2-0.5 mg; stannous chloride, 0.14-0.18 mg; potassium perrhenate, 0.005 mg; and [Re]ReO activity, 18.5-296 MBq, reacted for 30 min at 95°C with pH = 2. [Re]Re-IBA demonstrated good stability, high plasma protein binding rate, good hydrophilicity, and low toxicity. The biodistribution and bone imaging in normal animals showed rapid blood clearance, high bone uptake, low uptake in the solid organs and soft tissue, and high contrast during imaging. The biodistribution and imaging of bone metastasis in nude mice showed that [Re]Re-IBA has higher uptake in bone metastasis lesions than normal bone.
Our study encompassed the successful preparation of [Re]Re-IBA, a novel bone-seeking radiopharmaceutical, and confirmed it has potential in the treatment of bone metastasis and monitoring through imaging.
骨骼是恶性肿瘤转移的常见部位。有几种放射性药物可用于缓解癌症患者的骨痛。然而，每种放射性药物都有其自身的缺点，因此仍需要研究易于获得且具有高骨亲和力的放射性药物。伊班膦酸盐（IBA）和 Re 被用于标记以开发和评估一种新型的骨靶向放射性药物。
研究了 [Re]Re-IBA 的制备条件，并采用薄层层析法分析了放射性化学纯度。研究了[Re]Re-IBA 的稳定性、血浆蛋白结合率、脂水分配系数、正常小鼠的安全性和生物分布，以及新西兰兔的骨显像。此外，建立了裸鼠骨转移模型，研究了[Re]Re-IBA 在这些裸鼠中的生物分布和成像特征。
成功制备了放射性化学纯度>95%的[Re]Re-IBA。最佳制备条件为：IBA0.8-1.4mg；抗坏血酸 0.2-0.5mg；氯化亚锡 0.14-0.18mg；高铼酸钾 0.005mg；[Re]ReO4 活度 18.5-296MBq，在 95°C 下反应 30min，pH=2。[Re]Re-IBA 具有良好的稳定性、高血浆蛋白结合率、良好的亲水性和低毒性。正常动物的生物分布和骨显像显示，其具有快速的血液清除率、高骨摄取率、低固有机和软组织摄取率以及成像时的高对比度。裸鼠骨转移的生物分布和成像显示，[Re]Re-IBA 在骨转移病灶中的摄取量高于正常骨。
本研究成功制备了一种新型的骨靶向放射性药物[Re]Re-IBA，并通过成像证实其在治疗骨转移和监测方面具有潜力。
