Preliminary results of biodistribution and dosimetric analysis of [68Ga] Ga-DOTAZOL: a new zoledronate-based bisphosphonate for PET/CT diagnosis of bone diseases
Preliminary results of biodistribution and dosimetric analysis of [68Ga] Ga-DOTAZOL: a new zoledronate-based bisphosphonate for PET/CT diagnosis of bone diseases
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DOI：
10.1007/s12149-019-01348-7
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发表时间：
2019-06-01
影响因子：
2.6
通讯作者：
Bundschuh, Ralph. A.
中科院分区：
文献类型：
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作者：
Khawar, Ambreen;Eppard, Elisabeth;Bundschuh, Ralph. A.
目的68唑来膦酸镓（[Ga-68]Ga-DOTA（ZOL））作为一种有效的双膦酸盐，与[Lu-177]Lu-DOTA（ZOL）和[Ac-225]Ac-DOTA（ZOL）在骨疾病的PET/CT诊断中具有相似性。本研究旨在首次对[Ga-68]Ga-DOTA（ZOL）进行人体生物分布和剂量学分析。（平均年龄：72岁，男：女; 4：1）注射150- 190 MBq（4.05-5.14mCi）。用PET/CT初始动态显像研究[Ga-68] Ga-DOTA（ZOL）的生物分布;腹部的列表模式（重建为300秒的6个图像），然后在45分钟和2.5小时时使用Siemens Biograph 2 PET/CT相机进行静态（颅骨至大腿中部）成像。此外，在2.5小时内采集血样（8个时间点）和尿样（2个时间点）。使用访谈融合软件（MEDISO医学成像系统，布达佩斯，匈牙利）测定源器官中的总活性（MBq）。采用基于血液的方法测定骨髓自身剂量，采用梯形法计算膀胱内容物停留时间。采用OLINDA/EXM 2.0版软件（爱马仕Medical Solutions，斯德哥尔摩，Sweden）计算各靶器官的滞留时间、器官吸收剂量和有效剂量。定性和定量分析支持[Ga-68]Ga-DOTA（ZOL）的快速血液清除、高骨至软组织和病变至正常骨摄取。膀胱是最高吸收剂量的关键器官，其吸收剂量为0.368mSv/MBq，其次是成骨细胞、肾脏和红骨髓，其吸收剂量分别为0.040、0.031和0.027mSv/MBq。[Ga-68]Ga-DOTA（ZOL）的生物分布与[F-18]NaF、[Tc-99 m]Tc-MDP和[Ga-68]Ga-PSMA-617相当。通过适当的水合和利尿以减少膀胱和肾脏吸收剂量，由于其现场低成本生产和用于[Lu-177]Lu-DOTA（ZOL）和[Ac-225]Ac-DOTA（ZOL）治疗的个性化剂量测定的治疗诊断潜力，它具有明显优于[F-18]NaF的优势。
Objective Pre-clinical studies with gallium-68 zoledronate ([Ga-68]Ga-DOTA(ZOL)) have proposed it to be a potent bisphosphonate for PET/CT diagnosis of bone diseases and diagnostic counterpart to [Lu-177]Lu-DOTA(ZOL) and [Ac-225]Ac-DOTA(ZOL). This study aims to be the first human biodistribution and dosimetric analysis of [Ga-68]Ga-DOTA(ZOL).Methods Five metastatic skeletal disease patients (mean age: 72 years, M: F; 4:1) were injected with 150-190MBq (4.05-5.14mCi) of [Ga-68]Ga-DOTA(ZOL) i.v. Biodistribution of [Ga-68]Ga-DOTA(ZOL) was studied with PET/CT initial dynamic imaging for 30min; list mode over abdomen (reconstructed as six images of 300s) followed by static (skull to mid-thigh) imaging at 45min and 2.5h 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 2.5h. 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.Results 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-68]Ga-DOTA(ZOL). Urinary bladder with the highest absorbed dose of 0.368mSv/MBq presented the critical organ, followed by osteogenic cells, kidneys and red marrow receiving doses of 0.040, 0.031 and 0.027mSv/MBq, respectively. The mean effective dose was found to be 0.0174mSv/MBq which results in an effective dose of 2.61mSv from 150MBq.Conclusions Biodistribution of [Ga-68]Ga-DOTA(ZOL) was comparable to [F-18]NaF, [Tc-99m]Tc-MDP and [Ga-68]Ga-PSMA-617. With proper hydration and diuresis to reduce urinary bladder and kidney absorbed doses, it has clear advantages over [F-18]NaF owing to its onsite, low-cost production and theranostic potential of personalized dosimetry for treatment with [Lu-177]Lu-DOTA(ZOL) and [Ac-225]Ac-DOTA(ZOL).