一项评估Cu-NOTA-曲妥珠单抗作为乳腺癌患者正电子发射断层显像剂的初步临床试验。
A preliminary clinical trial to evaluate Cu-NOTA-Trastuzumab as a positron emission tomography imaging agent in patients with breast cancer.
作者信息
Lee Inki, Lim Ilhan, Byun Byung Hyun, Kim Byung Il, Choi Chang Woon, Woo Sang-Keun, Kim Kwang Il, Lee Kyo Chul, Kang Joo Hyun, Seong Min-Ki, Kim Hyun-Ah, Noh Woo Chul, Lim Sang Moo
机构信息
Department of Nuclear Medicine, Korea Cancer Centre Hospital, Korea Institute of Radiological and Medical Sciences, 75, Nowon-ro, Nowon-gu, Seoul, Korea.
Division of Applied RI, Research Institute of Radiological and Medical Sciences, Korea Institutes of Radiological and Medical Sciences, Seoul, Korea.
出版信息
EJNMMI Res. 2021 Jan 21;11(1):8. doi: 10.1186/s13550-021-00746-1.
BACKGROUND
The purpose of this study was to evaluate both the biodistribution and safety of Cu-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA)-Trastuzumab, a novel Cu-labeled positron emission tomography (PET) tracer for human epidermal growth factor receptor 2 (HER2) in patients with breast cancer.
METHODS
PET images at 1, 24, and 48 h after 296 MBq of Cu-NOTA-Trastuzumab injection were obtained from seven patients with breast cancer. Both the primary tumors' and metastatic lesions' maximum standardized uptake value (SUV) was evaluated. The mean SUV (SUV) was evaluated in the other organs, including the blood pool, liver, kidney, muscle, spleen, bladder, and the lungs, as well as the bones. Moreover, the internal radiation dosimetry was calculated using the OLINDA/EXM software. Safety was assessed based on feedback regarding adverse reactions and safety-related issues within 1 month after Cu-NOTA-Trastuzumab administration.
RESULTS
Cu-NOTA-Trastuzumab PET images showed that the overall SUV values in each organ negatively correlated with time. The liver's average SUV values were measured at 5.3 ± 0.7, 4.8 ± 0.6, and 4.4 ± 0.5 on 1 h, 24 h, and 48 h after injection, respectively. The average SUV blood values were measured at 13.1 ± 0.9, 9.1 ± 1.2, and 7.1 ± 1.9 on 1 h, 24 h, and 48 h after injection, respectively. The SUV of HER2-positive tumors was relatively higher than HER2-negative tumors (8.6 ± 5.1 and 5.2 ± 2.8 on 48 h after injection, respectively). Tumor-to-background ratios were higher in the HER2-positive tumors than in the HER2-negative tumors. No adverse events related to Cu-NOTA-Trastuzumab were reported. The calculated effective dose with a 296 MBq injection of Cu-NOTA-Trastuzumab was 2.96 mSv. The highest absorbed dose was observed in the liver (0.076 mGy/MBq), followed by the spleen (0.063 mGy/MBq), kidney (0.044 mGy/MBq), and heart wall (0.044 mGy/MBq).
CONCLUSIONS
Cu-NOTA-Trastuzumab showed a specific uptake at the HER2-expressing tumors, thus making it a feasible and safe monitoring tool of HER2 tumor status in patients with breast cancer.
TRIAL REGISTRATION
CRIS, KCT0002790. Registered 02 February 2018, https://cris.nih.go.kr.
背景
本研究旨在评估1,4,7-三氮杂环壬烷-1,4,7-三乙酸（NOTA）-曲妥珠单抗铜配合物这种新型的用于乳腺癌患者人表皮生长因子受体2（HER2）的铜标记正电子发射断层扫描（PET）示踪剂的生物分布和安全性。
方法
对7例乳腺癌患者注射296MBq的铜- NOTA -曲妥珠单抗后1、24和48小时进行PET成像。评估原发肿瘤和转移病灶的最大标准化摄取值（SUV）。对包括血池、肝脏、肾脏、肌肉、脾脏、膀胱、肺以及骨骼等其他器官的平均SUV进行评估。此外，使用OLINDA/EXM软件计算体内辐射剂量学。基于铜- NOTA -曲妥珠单抗给药后1个月内关于不良反应和安全相关问题的反馈评估安全性。
结果
铜- NOTA -曲妥珠单抗PET图像显示各器官的总体SUV值与时间呈负相关。注射后1小时、24小时和48小时肝脏的平均SUV值分别为5.3±0.7、4.8±0.6和4.4±0.5。注射后1小时、24小时和48小时血池的平均SUV值分别为13.1±0.9、9.1±1.2和7.1±1.9。HER2阳性肿瘤的SUV相对高于HER2阴性肿瘤（注射后48小时分别为8.6±5.1和5.2±2.8）。HER2阳性肿瘤的肿瘤与本底比值高于HER2阴性肿瘤。未报告与铜- NOTA -曲妥珠单抗相关的不良事件。注射296MBq铜- NOTA -曲妥珠单抗计算出的有效剂量为2.96mSv。肝脏的吸收剂量最高（0.076mGy/MBq），其次是脾脏（0.063mGy/MBq）、肾脏（0.044mGy/MBq）和心壁（0.044mGy/MBq）。
结论
铜- NOTA -曲妥珠单抗在HER2表达肿瘤处有特异性摄取，因此使其成为乳腺癌患者HER2肿瘤状态的一种可行且安全的监测工具。
试验注册
CRIS，KCT0002790。2018年2月2日注册，https://cris.nih.go.kr。
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