Assessment of Human Biodistribution and Dosimetry of 4-Fluoro-11β-Methoxy-16α-18F-Fluoroestradiol Using Serial Whole-Body PET/CT
Assessment of Human Biodistribution and Dosimetry of 4-Fluoro-11β-Methoxy-16α-18F-Fluoroestradiol Using Serial Whole-Body PET/CT
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DOI：
10.2967/jnumed.108.057000
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发表时间：
2009-01-01
影响因子：
9.3
通讯作者：
Benard, Francois
中科院分区：
文献类型：
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作者：
Beauregard, Jean-Mathieu;Croteau, Etienne;Benard, Francois
4-氟-11 β -甲氧基-16 α -f -18-氟雌二醇（4FMFES）是一种新开发的放射性标记雌二醇类似物，用于雌激素受体（er）的PET成像，在小动物模型中，与16 α -f -18-氟雌二醇（FES）相比，显示出更高的靶背景比。本研究的目的是评估4FMFES在健康女性中的生物分布、剂量学和安全性。方法：10名禁食的健康受试者（6名绝经前妇女和4名绝经后妇女）注射66-201 MBq高效比活性（中位数为251 GBq/mu mol）的4FMFES。在2小时内，每个受试者在PET/CT相机上进行4次连续快速PET采集和2次低剂量CT采集。在每次PET采集的源器官上绘制感兴趣的体积，允许计算时间-活性曲线，停留时间和辐射剂量学估计。获得一系列血液样本以测量血液和血浆活性清除率。通过血、尿分析和生命体征监测评估fmfes的安全性。结果：4FMFES注射液在所有受试者中耐受良好。肝脏呈高摄取，大量肝胆排泄。尿少。所有受试者的子宫摄取均可见，并随时间保持相对恒定（60分钟的最大和平均标准化摄取值分别为5.34 +/- 3.32和2.68 +/- 1.89）。背景活度低且随时间降低，导致子宫与背景比增加（60分钟时12.1 +/- 2.2）。主要脏器为胆囊（0.80 +/- 0.51 mGy/MBq），其次为上大肠（0.13 +/- 0.04 mGy/MBq）、小肠（0.12 +/- 0.04 mGy/MBq）和肝脏（0095 +/- 0.019 mGy/MBq）。对于典型的4FMFES剂量185 MBq，计算出的有效剂量为4.82 +/- 0.70 mSv。结论：4FMFES被认为是安全的，其有效剂量仍在可接受的范围内。胆囊吸收剂量相对较高，在未禁食的患者中注射4FMFES可能会降低胆囊吸收剂量。在绝经前和绝经后的受试者中，fmfes显示了显著的、潜在的雌激素受体介导的子宫摄取。
4-Fluoro-11 beta-methoxy-16 alpha-F-18-fluoroestradiol (4FMFES) is a newly developed radiolabeled estradiol analog for PET imaging of estrogen receptors (ERs) that shows improved target-to-background ratios, compared with 16 alpha-F-18-fluoroestradiol (FES), in small-animal models. The aim of this study was to assess the biodistribution, dosimetry, and safety of 4FMFES in healthy women. Methods: Ten healthy subjects (6 pre- and 4 postmenopausal women) who had fasted were injected with 66-201 MBq of 4FMFES at a high effective specific activity (median, 251 GBq/mu mol). During a 2-h period, each subject underwent 4 serial rapid PET acquisitions and 2 low-dose CT acquisitions on a PET/CT camera. Volumes of interest were drawn over source organs for each PET acquisition, allowing the calculation of time-activity curves, residence times, and radiation dosimetry estimates. Serial blood samples were obtained to measure blood and plasma activity clearance. 4FMFES safety was assessed by blood and urine analyses and vital-sign monitoring. Results: A 4FMFES injection was well tolerated in all subjects. The liver showed high uptake, and the hepatobiliary excretion was massive. Little urinary excretion occurred. Uterus uptake was visualized in all subjects and remained relatively constant over time (maximum and mean standardized uptake values at 60 min were 5.34 +/- 3.32 and 2.68 +/- 1.89, respectively). Background activity was low and decreased over time, resulting in an increasing uterus-to-background ratio (12.1 +/- 2.2 at 60 min). The critical organ was the gallbladder (0.80 +/- 0.51 mGy/MBq), followed by the upper large intestine (0.13 +/- 0.04 mGy/MBq), small intestine (0.12 +/- 0.04 mGy/MBq), and liver (0095 +/- 0.019 mGy/MBq). For a typical 4FMFES dose of 185 MBq, the effective dose was calculated at 4.82 +/- 0.70 mSv. Conclusion: 4FMFES is considered safe for use in humans, and its effective dose remains well within acceptable limits. The absorbed dose to the gallbladder was relatively high and could potentially be reduced by injecting 4FMFES in patients who had not fasted. 4FMFES showed a significant, potentially estrogen receptor-mediated uterus uptake in both pre- and postmenopausal subjects.