Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET.
Functional imaging of human epidermal growth factor receptor 2-positive metastatic breast cancer using (64)Cu-DOTA-trastuzumab PET.
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使用 (64)Cu-DOTA-曲妥珠单抗 PET 对人表皮生长因子受体 2 阳性转移性乳腺癌进行功能成像。
DOI：
10.2967/jnumed.113.122630
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发表时间：
2014-01
期刊：
影响因子：
--
通讯作者：
Raubitschek AA
中科院分区：
文献类型：
--
作者：
Mortimer JE;Bading JR;Colcher DM;Conti PS;Frankel PH;Carroll MI;Tong S;Poku E;Miles JK;Shively JE;Raubitschek AA
患有人表皮生长因子受体 2 (HER2) 阳性乳腺癌的女性适合接受抗 HER2 抗体曲妥珠单抗治疗。复发性疾病中 HER2 状态的评估通常是通过对单个病变进行空心针活检来进行的，该病变可能不能代表较大的肿瘤块或其他疾病部位。我们的长期目标是开发放射性标记曲妥珠单抗的正电子发射断层扫描 (PET)，用于系统评估肿瘤 HER2 表达并确定抗 HER2 疗法的适当使用。本研究的目的是评估 64Cu-DOTA-曲妥珠单抗的 PET-CT 用于检测和测量 HER2 阳性转移性乳腺癌患者曲妥珠单抗的肿瘤摄取。 8 名活检确诊为 HER2 阳性转移性乳腺癌且 ≥ 4 个月未接受抗 HER2 治疗的女性接受了完整分期，包括 18F-氟脱氧葡萄糖 (FDG)/PET-CT。对于 8 名患者中的 6 名，在注射 64Cu-DOTA-曲妥珠单抗（364-512 MBq，5 mg 曲妥珠单抗）之前输注曲妥珠单抗（45 mg）。注射 64Cu-DOTA-曲妥珠单抗后 21-25（“第 1 天”）和 47-49（“第 2 天”）小时进行 PET-CT（PET 扫描持续时间 1 小时）。根据 18F-FDG/PET-CT 选择扫描视野。 PET 上相对于邻近组织可见的病变被认为是 PET 阳性；分析仅限于 CT 可识别的病变。显着病变中的放射性标记摄取被测量为最大单体素标准化摄取值（SUVmax）。预给药 45 mg 曲妥珠单抗后，肝脏对 64Cu 的摄取减少了约 75%，但对肿瘤摄取没有显着影响。该研究包括 89 个 CT 阳性病变；第 1 天、第 2 天和 18F-FDG 的检测灵敏度分别为 77%、89% 和 93%。平均而言，64Cu-DOTA-曲妥珠单抗和 18F-FDG 的肿瘤摄取相似 [SUVmax（平均值，范围）：第 1 天（8.1、3.0-22.5，n=48）；第 2 天（8.9，0.9-28.9，n=38）； 18F-FDG (9.7, 3.3-25.4, n=56)]，但两种放射性示踪剂之间相同病变摄取的程度不相关。未观察到毒性，64Cu-DOTA-曲妥珠单抗的估计辐射剂量与 18F-FDG 相似。 64Cu-DOTA-曲妥珠单抗以高灵敏度可视化 HER2 阳性转移性乳腺癌，并可有效调查播散性疾病。 45 mg 曲妥珠单抗预剂量提供了有利于肿瘤成像的 64Cu-DOTA-曲妥珠单抗生物分布。 64Cu-DOTA-曲妥珠单抗/PET-CT 值得进一步评估，以评估肿瘤 HER2 表达并测量基于曲妥珠单抗的治疗的实施。
Women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are candidates for treatment with the anti-HER2 antibody trastuzumab. Assessment of HER2 status in recurrent disease is usually made by core needle biopsy of a single lesion which may not be representative of the larger tumor mass or other sites of disease. Our long-range goal is to develop positron emission tomography (PET) of radiolabeled trastuzumab for systemically assessing tumor HER2 expression and identifying appropriate use of anti-HER2 therapies. The purpose of this study was to evaluate PET-CT of 64Cu-DOTA-trastuzumab for detecting and measuring tumor uptake of trastuzumab in patients with HER2-positive metastatic breast cancer. Eight women with biopsy-confirmed HER2-positive metastatic breast cancer and no anti-HER2 therapy for ≥ 4 mo underwent complete staging, including 18F-fluorodeoxyglucose (FDG)/PET-CT. For 6 of the 8 patients, 64Cu-DOTA-trastuzumab injection (364-512 MBq, 5 mg trastuzumab) was preceded by trastuzumab infusion (45 mg). PET-CT (PET scan duration 1 h) was performed 21-25 (“Day 1”) and 47-49 (“Day 2”) h after 64Cu-DOTA-trastuzumab injection. Scan fields of view were chosen based on 18F-FDG/PET-CT. Lesions visualized relative to adjacent tissue on PET were considered PET-positive; analysis was limited to lesions identifiable on CT. Radiolabel uptake in prominent lesions was measured as maximum single-voxel standardized uptake value (SUVmax). Liver uptake of 64Cu was reduced approximately 75% with the 45 mg trastuzumab pre-dose, without significant effect on tumor uptake. The study included 89 CT-positive lesions; detection sensitivity was 77, 89 and 93% for Day 1, Day 2 and 18F-FDG, respectively. On average, tumor uptake was similar for 64Cu-DOTA-trastuzumab and 18F-FDG [SUVmax (mean, range): Day 1 (8.1, 3.0-22.5, n=48); Day 2 (8.9, 0.9-28.9, n=38); 18F-FDG (9.7, 3.3-25.4, n=56)], but the extent of same-lesion uptake was not correlated between the 2 radiotracers. No toxicities were observed, and estimated radiation dose from 64Cu-DOTA-trastuzumab was similar to 18F-FDG. 64Cu-DOTA-trastuzumab visualizes HER2-positive metastatic breast cancer with high sensitivity, and is effective in surveying disseminated disease. A 45 mg trastuzumab pre-dose provides a 64Cu-DOTA-trastuzumab biodistribution favorable for tumor imaging. 64Cu-DOTA-trastuzumab/PET-CT warrants further evaluation for assessing tumor HER2 expression and measuring delivery of trastuzumab-based therapy.
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DOI：
10.1093/jnci/93.15.1141
发表时间：
2001-08-01
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Simon, R;Nocito, A;Sauter, G
通讯作者：
Sauter, G
影响因子：
45.3
作者：
Perik, Patrick J.;Lub-De Hooge, Marjolijn N.;de Vries, Elisabeth G. E.
通讯作者：
de Vries, Elisabeth G. E.
影响因子：
56.9
作者：
SLAMON, DJ;CLARK, GM;MCGUIRE, WL
通讯作者：
MCGUIRE, WL
影响因子：
11.8
作者：
Hurvitz, Sara A.;Hu, Yufang;O'Brien, Neil;Finn, Richard S.
通讯作者：
Finn, Richard S.
影响因子：
4.7
作者：
Li, Lin;Bading, James;Shively, John E.
通讯作者：
Shively, John E.