As a growing number of patients with multiple myeloma (MM) respond to upfront therapies while eventually relapsing in a time frame that is often unpredictable, attention has increasingly focused on developing novel diagnostic criteria to also account for disease dissemination. Positron emission tomography/computed tomography (PET/CT) is often used as a noninvasive monitoring strategy to assess cancer cell dissemination, but because the uptake of the currently used radiotracer 18fluorodeoxyglucose (18F-FDG) is a function of the metabolic activity of both malignant and nonmalignant cells, the results frequently lack sufficient specificity. Radiolabeled antibodies targeting MM tissue may detect disease irrespective of cell metabolism. Hence, we conjugated the clinically significant CD38-directed human antibody daratumumab (Darzalex [Dara]) to the DOTA chelator and labeled it with the positron-emitting radionuclide copper 64 (64Cu; 64Cu-DOTA-Dara). Here, we show that 64Cu-DOTA-Dara can efficiently bind CD38 on the surface of MM cells and was mainly detected in the bones associated with tumor in a MM murine model. We also show that PET/CT based on 64Cu-DOTA-Dara displays a higher resolution and specificity to detect MM cell dissemination than does 18F-FDG PET/CT and was even more sensitive than were bioluminescence signals. We therefore have supporting evidence for using 64Cu-DOTA-Dara as a novel imaging agent for MM.

中文翻译：

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铜 64 标记的达雷妥尤单抗作为多发性骨髓瘤的 PET/CT 成像示踪剂

随着越来越多的多发性骨髓瘤 (MM) 患者对前期治疗有反应，但最终在通常不可预测的时间范围内复发，注意力越来越集中在开发新的诊断标准上，以解释疾病的传播。正电子发射断层扫描/计算机断层扫描 (PET/CT) 常被用作评估癌细胞扩散的无创监测策略，但因为目前使用的放射性示踪剂 18 氟脱氧葡萄糖 (18F-FDG) 的摄取是两种恶性细胞代谢活动的函数。和非恶性细胞，结果往往缺乏足够的特异性。无论细胞代谢如何，靶向 MM 组织的放射性标记抗体都可以检测疾病。因此，我们将具有临床意义的 CD38 导向人抗体达雷妥尤单抗 (Darzalex [Dara]) 与 DOTA 螯合剂偶联，并用正电子发射放射性核素铜 64 (64Cu；64Cu-DOTA-Dara) 对其进行标记。在这里，我们表明 64Cu-DOTA-Dara 可以有效地结合 MM 细胞表面的 CD38，并且主要在 MM 小鼠模型中与肿瘤相关的骨骼中检测到。我们还表明，基于 64Cu-DOTA-Dara 的 PET/CT 显示出比 18F-FDG PET/CT 更高的分辨率和特异性来检测 MM 细胞传播，并且比生物发光信号更敏感。因此，我们有支持使用 64Cu-DOTA-Dara 作为 MM 的新型显像剂的证据。我们表明 64Cu-DOTA-Dara 可以有效地结合 MM 细胞表面的 CD38，并且主要在 MM 小鼠模型中与肿瘤相关的骨骼中检测到。我们还表明，基于 64Cu-DOTA-Dara 的 PET/CT 显示出比 18F-FDG PET/CT 更高的分辨率和特异性来检测 MM 细胞传播，并且比生物发光信号更敏感。因此，我们有支持使用 64Cu-DOTA-Dara 作为 MM 的新型显像剂的证据。我们表明 64Cu-DOTA-Dara 可以有效地结合 MM 细胞表面的 CD38，并且主要在 MM 小鼠模型中与肿瘤相关的骨骼中检测到。我们还表明，基于 64Cu-DOTA-Dara 的 PET/CT 显示出比 18F-FDG PET/CT 更高的分辨率和特异性来检测 MM 细胞传播，并且比生物发光信号更敏感。因此，我们有支持使用 64Cu-DOTA-Dara 作为 MM 的新型显像剂的证据。