Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64-labeled daratumumab
Identifying CD38+ cells in patients with multiple myeloma: first-in-human imaging using copper-64-labeled daratumumab
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DOI：
10.1182/bloodadvances.2020002603
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发表时间：
2020-10-27
期刊：
影响因子：
7.5
通讯作者：
Pichiorri, Flavia
中科院分区：
文献类型：
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作者：
Krishnan, Amrita;Adhikarla, Vikram;Pichiorri, Flavia
f -18-氟脱氧葡萄糖（FDG）正电子发射断层扫描/计算机断层扫描（PET/CT）是检测多发性骨髓瘤（MM）最广泛使用的成像技术之一。细胞内FDG摄取描述了体内代谢活动，在恶性和非恶性细胞中都可以看到，导致敏感性和特异性有限。我们的研究小组在临床前表明，使用cd38导向的人抗体daratumumab通过螯合剂DOTA （Cu-64-daratumumab）与Cu-64放射结合，追踪MM传播，导致比FDG更高的敏感性和特异性。在这里，我们报告了一项i期试验的结果，该试验旨在(1)评估Cu-64-daratumumab PET/CT的安全性和可行性，(2)初步评估和表征Cu-64-daratumumab准确检测或排除MM病变的能力。共有12例daratumumab初治患者接受影像学检查。在注射15 mCi/5 mg Cu-64-daratumumab之前，患者分别接受0 （n = 3）、10 （n = 3）、45 （n = 3）或95 mg （n = 3）未标记的daratumumab治疗，以评估其对图像质量的影响。未标记的达拉图单抗或cu -64达拉图单抗均未观察到显著不良事件。在测试的剂量水平中，45mg未标记的daratumumab在去除背景信号而不使靶点饱和方面是最理想的。Cu-64-daratumumab PET/CT为MM提供了安全的全身成像。计划进行一项试验，比较Cu-64-daratumumab PET/CT与FDG PET/CT的敏感性和特异性。该试验在www.clinicaltrials.gov上注册为#NCT03311828。
F-18-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is one of the most widely used imaging techniques to detect multiple myeloma (MM). Intracellular FDG uptake depicts in vivo metabolic activity, which can be seen in both malignant and nonmalignant cells, resulting in limited sensitivity and specificity. Our group showed preclinically that tracing MM dissemination using a CD38-directed human antibody, daratumumab, that is radioconjugated with Cu-64 via the chelator DOTA (Cu-64-daratumumab), led to improved sensitivity and specificity over that of FDG. Here, we report the results of a phase 1 trial designed to (1) assess the safety and feasibility of Cu-64-daratumumab PET/CT and (2) preliminarily evaluate and characterize the ability of Cu-64-daratumumab to accurately detect or exclude MM lesions. A total of 12 daratumumab-naive patients were imaged. Prior to the injection of 15 mCi/5 mg of Cu-64-daratumumab, patients were treated with 0 (n = 3), 10 (n = 3), 45 (n = 3), or 95 mg (n = 3) of unlabeled daratumumab to assess its effect on image quality. No significant adverse events were observed from either unlabeled daratumumab or Cu-64-daratumumab. Of the dose levels tested, 45 mg unlabeled daratumumab was the most optimal in terms of removing background signal without saturating target sites. Cu-64-daratumumab PET/CT provided safe whole-body imaging of MM. A trial comparing the sensitivity and specificity of Cu-64-daratumumab PET/CT with that of FDG PET/CT is planned. This trial was registered at www.clinicaltrials.gov as #NCT03311828.