Department of Nuclear Medicine, Institute of Clinical Nuclear Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200127, China.
Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Mol Pharm. 2022 Oct 3;19(10):3492-3501. doi: 10.1021/acs.molpharmaceut.1c00628. Epub 2021 Nov 29.
B cell maturation antigen (BCMA) is a promising theranostic target for multiple myeloma (MM). BCMA-targeted therapeutics, such as antibody-drug conjugates and chimeric antigen receptor T-cell immunotherapies, are rapidly reshaping the treatment landscape of MM. Along with the progress, a critical challenge is to noninvasively visualize the dynamic change of BCMA for a better-personalized prescription of the above-mentioned therapeutics. We aim to develop immuno-positron emission tomography (immunoPET) imaging strategies to visualize BCMA expression and realize target-specific diagnosis of MM in the work. A series of BCMA-targeting nanobodies were produced and two of them were successfully labeled with gallium-68 (Ga). MM models were established using MM.1S cell line and NOD-PrkdcIl2rg/Nju mice. The diagnostic efficacies of the developed probes (i.e., [Ga]Ga-NOTA-MMBC2 and [Ga]Ga-NOTA-MMBC3) were investigated in disseminated MM models by immunoPET imaging, region of interest analysis on PET images, biodistribution study, and histopathological staining study. [Ga]Ga-NOTA-MMBC2 and [Ga]Ga-NOTA-MMBC3 were developed with radiochemical purities of >99%. ImmunoPET imaging with either [Ga]Ga-NOTA-MMBC2 or [Ga]Ga-NOTA-MMBC3 precisely visualized BCMA expression and delineated MM lesions throughout the bone marrows. Moreover, [Ga]Ga-NOTA-MMBC3 immunoPET successfully detected remnant MM after treatment with daratumumab, a prescription medicine used to treat MM. The immunoPET imaging data correlated well with the biodistribution and immunohistochemistry staining results. The work successfully developed two state-of-the-art BCMA-targeted radiotracers for annotating BCMA expression and diagnosing MM. Translational studies interpreting the diagnostic efficacies of the immunoPET radiotracers are warranted.
B 细胞成熟抗原（BCMA）是多发性骨髓瘤（MM）有前途的治疗靶点。BCMA 靶向治疗药物，如抗体药物偶联物和嵌合抗原受体 T 细胞免疫疗法，正在迅速改变 MM 的治疗格局。随着进展，一个关键的挑战是无创可视化 BCMA 的动态变化，以更好地为上述治疗方法进行个性化处方。我们旨在开发免疫正电子发射断层扫描（immunoPET）成像策略，以可视化 BCMA 表达并实现 MM 的靶向特异性诊断。我们生产了一系列 BCMA 靶向纳米抗体，并成功地用镓-68（Ga）标记了其中两种。使用 MM.1S 细胞系和 NOD-PrkdcIl2rg/Nju 小鼠建立 MM 模型。通过 immunoPET 成像、PET 图像的感兴趣区分析、生物分布研究和组织病理学染色研究，研究了开发的探针（即 [Ga]Ga-NOTA-MMBC2 和 [Ga]Ga-NOTA-MMBC3）在弥散性 MM 模型中的诊断效果。[Ga]Ga-NOTA-MMBC2 和 [Ga]Ga-NOTA-MMBC3 的放射化学纯度均>99%。用 [Ga]Ga-NOTA-MMBC2 或 [Ga]Ga-NOTA-MMBC3 进行 immunoPET 成像，精确地可视化了 BCMA 表达，并描绘了整个骨髓中的 MM 病变。此外，[Ga]Ga-NOTA-MMBC3 immunoPET 成功检测到达雷木单抗治疗后的残留 MM，达雷木单抗是一种用于治疗 MM 的处方药。免疫 PET 成像数据与生物分布和免疫组织化学染色结果高度相关。该工作成功开发了两种最先进的 BCMA 靶向放射性示踪剂，用于注释 BCMA 表达和诊断 MM。需要进行翻译研究来解释 immunoPET 放射性示踪剂的诊断效果。
