PDF(Pubmed)
Abstract：
BACKGROUND: We designed and synthesized a novel bisphosphonate radiopharmaceutical (68 Ga- or 177Lu-labeled DOTA-ibandronate [68 Ga/177Lu-DOTA-IBA]) for the targeted diagnosis and treatment of bone metastases. The biodistribution and internal dosimetry of a single therapeutic dose of 177Lu-DOTA-IBA were evaluated using a series of single-photon emission computerized tomography (SPECT) images and blood samples. Five patients with multiple bone metastases were included in this prospective study. After receiving 1110 MBq 177Lu-DOTA-IBA, patients underwent whole-body planar, SPECT/CT imaging and venous blood sampling over 7 days. Dosimetric evaluation was performed for the main organs and tumor lesions. Safety was assessed using blood biomarkers.
RESULTS: 177Lu-DOTA-IBA showed fast uptake, high retention in bone lesions, and rapid clearance from the bloodstream in all patients. In this cohort, the average absorbed doses (ADs) in the bone tumor lesions, kidneys, liver, spleen, red marrow, bladder-wall, and osteogenic cells were 5.740, 0.114, 0.095, 0.121, 0.095, and 0.333 Gy/GBq, respectively. Although no patient reached the predetermined dose thresholds, the red marrow will be the dose-limiting organ. There were no adverse reactions recorded after the administration of 1110 MBq 177Lu-DOTA-IBA.
CONCLUSIONS: Dosimetric results show that the ADs for critical organs and total body are within the safety limit and with high bone retention. It is a promising radiopharmaceutical alternative for the targeted treatment of bone metastases, controlling its progression, and improving the survival and quality of life of patients with advanced bone metastasis.
RESULTS: 177Lu-DOTA-IBA showed fast uptake, high retention in bone lesions, and rapid clearance from the bloodstream in all patients. In this cohort, the average absorbed doses (ADs) in the bone tumor lesions, kidneys, liver, spleen, red marrow, bladder-wall, and osteogenic cells were 5.740, 0.114, 0.095, 0.121, 0.095, and 0.333 Gy/GBq, respectively. Although no patient reached the predetermined dose thresholds, the red marrow will be the dose-limiting organ. There were no adverse reactions recorded after the administration of 1110 MBq 177Lu-DOTA-IBA.
CONCLUSIONS: Dosimetric results show that the ADs for critical organs and total body are within the safety limit and with high bone retention. It is a promising radiopharmaceutical alternative for the targeted treatment of bone metastases, controlling its progression, and improving the survival and quality of life of patients with advanced bone metastasis.
摘要：
背景：我们设计并合成了一种新型的双磷酸盐放射性药物（68Ga-或177Lu-标记的DOTA-伊班膦酸盐[68Ga/177Lu-DOTA-IBA]），用于骨转移的靶向诊断和治疗。使用一系列单光子发射计算机断层扫描（SPECT）图像和血液样本评估了单治疗剂量177Lu-DOTA-IBA的生物分布和内部剂量测定。这项前瞻性研究包括5例多发性骨转移患者。收到1110MBq177Lu-DOTA-IBA后，患者接受全身平面，SPECT/CT成像和静脉采血超过7天。对主要器官和肿瘤病变进行剂量学评估。使用血液生物标志物评估安全性。
结果：177Lu-DOTA-IBA显示快速摄取，在骨病变中高度保留，并迅速从所有患者的血液中清除。在这个队列中，骨肿瘤病变的平均吸收剂量（ADs），肾脏，肝脏,脾,脾红骨髓,膀胱壁,成骨细胞分别为5.740、0.114、0.095、0.121、0.095和0.333Gy/GBq,分别。虽然没有病人达到预定的剂量阈值，红骨髓将是剂量限制器官。使用1110MBq177Lu-DOTA-IBA后无不良反应。
结论：剂量学结果表明，关键器官和全身的AD均在安全范围内，并且具有较高的骨保留率。它是骨转移的靶向治疗的一种有前途的放射性药物替代品，控制它的发展，提高晚期骨转移患者的生存和生活质量。
结果：177Lu-DOTA-IBA显示快速摄取，在骨病变中高度保留，并迅速从所有患者的血液中清除。在这个队列中，骨肿瘤病变的平均吸收剂量（ADs），肾脏，肝脏,脾,脾红骨髓,膀胱壁,成骨细胞分别为5.740、0.114、0.095、0.121、0.095和0.333Gy/GBq,分别。虽然没有病人达到预定的剂量阈值，红骨髓将是剂量限制器官。使用1110MBq177Lu-DOTA-IBA后无不良反应。
结论：剂量学结果表明，关键器官和全身的AD均在安全范围内，并且具有较高的骨保留率。它是骨转移的靶向治疗的一种有前途的放射性药物替代品，控制它的发展，提高晚期骨转移患者的生存和生活质量。
