LAGEPP Université Claude Bernard Lyon 1, CNRS UMR5007, Villeurbanne, France.
Université Paris-Saclay, CNRS UMR 8612, Institut Galien Paris-Saclay, France.
Adv Healthc Mater. 2022 Jan;11(2):e2101565. doi: 10.1002/adhm.202101565. Epub 2021 Nov 7.
Current clinical imaging modalities for the sensitive and specific detection of multiple myeloma (MM) rely on nonspecific imaging contrast agents based on gadolinium chelates for magnetic resonance imaging (MRI) or for F-FDG-directed and combined positron emission tomography (PET) and computed tomography (CT) scans. These tracers are not, however, able to detect minute plasma cell populations in the tumor niche, leading to false negative results. Here, a novel PET-based anti-BCMA nanoplatform labeled with Cu is developed to improve the monitoring of these cells in both the spine and femur and to compare its sensitivity and specificity to more conventional immunoPET ( Cu labeled anti-BCMA antibody) and passively targeted PET radiotracers ( CuCl and F-FDG). This proof-of-concept preclinical study confirmed that by conjugating up to four times more radioisotopes per antibody with the immuno-nanoPET platform, an improvement in the sensitivity and in the specificity of PET to detect tumor cells in an orthotopic model of MM is observed when compared to the traditional immunoPET approach. It is anticipated that when combined with tumor biopsy, this immuno-nanoPET platform may improve the management of patients with MM.
目前,用于敏感和特异性检测多发性骨髓瘤(MM)的临床成像方式依赖于基于镧系螯合物的非特异性成像对比剂,用于磁共振成像(MRI)或 F-FDG 导向的正电子发射断层扫描(PET)和计算机断层扫描(CT)扫描。然而,这些示踪剂无法检测肿瘤微环境中的微小浆细胞群,导致假阴性结果。在这里,开发了一种新型基于 PET 的抗 BCMA 纳米平台,用 64Cu 标记,以提高对脊柱和股骨中这些细胞的监测,并将其敏感性和特异性与更传统的免疫 PET(用 64Cu 标记的抗 BCMA 抗体)和被动靶向 PET 放射性示踪剂(64CuCl 和 F-FDG)进行比较。这项概念验证性临床前研究证实,通过将多达四倍的放射性同位素与免疫纳米 PET 平台结合,与传统的免疫 PET 方法相比,在 MM 的原位模型中观察到 PET 检测肿瘤细胞的敏感性和特异性得到提高。预计当与肿瘤活检相结合时,这种免疫纳米 PET 平台可能会改善 MM 患者的治疗管理。