Department of Nuclear Medicine, University Medical Center Bonn, Bonn, Germany.
Institute of Nuclear Chemistry, Johannes Gutenberg-University Mainz, Mainz, Germany.
Ann Nucl Med. 2019 Jun;33(6):404-413. doi: 10.1007/s12149-019-01348-7. Epub 2019 Mar 15.
Pre-clinical studies with gallium-68 zoledronate ([Ga]Ga-DOTA) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic counterpart to [Lu]Lu-DOTA and [Ac]Ac-DOTA. This study aims to be the first human biodistribution and dosimetric analysis of [Ga]Ga-DOTA.
Five metastatic skeletal disease patients (mean age: 72 years, M: F; 4:1) were injected with 150-190 MBq (4.05-5.14 mCi) of [Ga]Ga-DOTA i.v. Biodistribution of [Ga]Ga-DOTA was studied with PET/CT initial dynamic imaging for 30 min; list mode over abdomen (reconstructed as six images of 300 s) followed by static (skull to mid-thigh) imaging at 45 min and 2.5 h with Siemens Biograph 2 PET/CT camera. Also, blood samples (8 time points) and urine samples (2 time points) were collected over a period of 2.5 h. Total activity (MBq) in source organs was determined using interview fusion software (MEDISO Medical Imaging Systems, Budapest, Hungary). A blood-based method for bone marrow self-dose determination and a trapezoidal method for urinary bladder contents residence time calculation were used. OLINDA/EXM version 2.0 software (Hermes Medical Solutions, Stockholm, Sweden) was used to generate residence times for source organs, organ absorbed doses and effective doses.
High uptake in skeleton as target organ, kidneys and urinary bladder as organs of excretion and faint uptake in liver, spleen and salivary glands were seen. Qualitative and quantitative analysis supported fast blood clearance, high bone to soft tissue and lesion to normal bone uptake with [Ga]Ga-DOTA. Urinary bladder with the highest absorbed dose of 0.368 mSv/MBq presented the critical organ, followed by osteogenic cells, kidneys and red marrow receiving doses of 0.040, 0.031 and 0.027 mSv/MBq, respectively. The mean effective dose was found to be 0.0174 mSv/MBq which results in an effective dose of 2.61 mSv from 150 MBq.
Biodistribution of [Ga]Ga-DOTA was comparable to [F]NaF, [Tc]Tc-MDP and [Ga]Ga-PSMA-617. With proper hydration and diuresis to reduce urinary bladder and kidney absorbed doses, it has clear advantages over [F]NaF owing to its onsite, low-cost production and theranostic potential of personalized dosimetry for treatment with [Lu]Lu-DOTA and [Ac]Ac-DOTA.
镓-68 唑来膦酸盐 ([Ga]Ga-DOTA) 的临床前研究表明，它是一种用于 PET/CT 诊断骨疾病的有效双膦酸盐，是 [Lu]Lu-DOTA 和 [Ac]Ac-DOTA 的诊断对应物。本研究旨在对 [Ga]Ga-DOTA 进行首次人体生物分布和剂量学分析。
5 例转移性骨疾病患者（平均年龄：72 岁，男：女；4:1）静脉注射 150-190 MBq（4.05-5.14 mCi）[Ga]Ga-DOTA。使用 PET/CT 初始动态成像在 30 分钟内研究 [Ga]Ga-DOTA 的生物分布；腹部列表模式（重建为 300 s 的 6 个图像），然后在 45 分钟和 2.5 小时进行静态（颅骨至大腿中部）成像，使用西门子 Biograph 2 PET/CT 相机。此外，在 2.5 小时内采集血液样本（8 个时间点）和尿液样本（2 个时间点）。使用访谈融合软件（匈牙利布达佩斯 MEDISO Medical Imaging Systems）确定源器官中的总活动（MBq）。使用基于血液的骨髓自剂量测定方法和梯形方法计算膀胱内容物停留时间。使用 OLINDA/EXM 版本 2.0 软件（瑞典斯德哥尔摩 Hermes Medical Solutions）生成源器官的停留时间、器官吸收剂量和有效剂量。
在骨骼作为靶器官、肾脏和膀胱作为排泄器官中观察到高摄取，在肝脏、脾脏和唾液腺中观察到低摄取。定性和定量分析支持 [Ga]Ga-DOTA 具有快速的血液清除率、高骨与软组织和病变与正常骨摄取率。吸收剂量最高的膀胱为临界器官，随后是成骨细胞、肾脏和红骨髓，吸收剂量分别为 0.040、0.031 和 0.027 mSv/MBq。发现平均有效剂量为 0.0174 mSv/MBq，这导致从 150 MBq 中获得 2.61 mSv 的有效剂量。
[Ga]Ga-DOTA 的生物分布与 [F]NaF、[Tc]Tc-MDP 和 [Ga]Ga-PSMA-617 相当。通过适当的水合和利尿来降低膀胱和肾脏的吸收剂量，与 [F]NaF 相比，它具有明显的优势，因为它具有现场、低成本的生产能力，并且具有 [Lu]Lu-DOTA 和 [Ac]Ac-DOTA 治疗的个性化剂量学治疗潜力。
