开发基于肽的新型 PET 示踪剂[68Ga]Ga-DOTA-BP1,用于检测多发性骨髓瘤中的 BCMA

IF 6.8 1区 医学 Q1 CHEMISTRY, MEDICINAL
Lele Song, Sujun Jiang, Qi Yang, Wenpeng Huang, Yongkang Qiu, Zhao Chen, Xinyao Sun, Tianyao Wang, Sitong Wu, Yongshou Chen, Huajie Zeng, Zihua Wang* and Lei Kang*, 
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引用次数: 0

摘要

B细胞成熟抗原(BCMA)已成为诊断和治疗多发性骨髓瘤的一种有前途的肿瘤标志物。体内 BCMA 表达的无创、快速检测为筛查和评估接受 BCMA 靶向治疗的多发性骨髓瘤患者提供了重要价值。我们采用高通量微阵列策略,从一珠一化合物(OBOC)肽库中鉴定出了BCMA靶向肽BP1。通过表面等离子体共振成像(SPRi)、流式细胞术和共聚焦成像评估了BP1的BCMA靶向特异性和亲和力。建立了 BCMA 阳性(H929)和 BCMA 阴性(K562)皮下肿瘤模型,并用 68Ga 标记了 BP1,随后进行了 PET 成像和生物分布研究。PET 成像显示,68Ga 标记的 BP1 在多发性骨髓瘤中具有显著的特异性摄取,能够快速识别 BCMA 表达并精确划分疾病。因此,BP1 是多发性骨髓瘤成像的理想候选药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Development of a Novel Peptide-Based PET Tracer [68Ga]Ga-DOTA-BP1 for BCMA Detection in Multiple Myeloma

Development of a Novel Peptide-Based PET Tracer [68Ga]Ga-DOTA-BP1 for BCMA Detection in Multiple Myeloma

B-cell maturation antigen (BCMA) has emerged as a promising tumor marker for the diagnosis and treatment of multiple myeloma. The noninvasive and rapid detection of BCMA expression in vivo provides significant value in screening and evaluating multiple myeloma patients receiving BCMA-targeted therapy. We identified the BCMA-targeting peptide BP1 from a one-bead-one-compound (OBOC) peptide library using a high-throughput microarray strategy. The BCMA-targeting specificity and affinity of BP1 were assessed by surface plasmon resonance imaging (SPRi), flow cytometry, and confocal imaging. BCMA-positive (H929) and BCMA-negative (K562) subcutaneous tumor models were established and labeled with 68Ga for BP1, followed by PET imaging and biodistribution studies. PET imaging demonstrated that 68Ga-labeled BP1 has significant specific uptake in multiple myeloma, enabling rapid identification of BCMA expression and precise delineation of the disease. Thus, BP1 represents an ideal candidate for multiple myeloma imaging.

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来源期刊
Journal of Medicinal Chemistry
Journal of Medicinal Chemistry 医学-医药化学
CiteScore
4.00
自引率
11.00%
发文量
804
审稿时长
1.9 months
期刊介绍: The Journal of Medicinal Chemistry is a prestigious biweekly peer-reviewed publication that focuses on the multifaceted field of medicinal chemistry. Since its inception in 1959 as the Journal of Medicinal and Pharmaceutical Chemistry, it has evolved to become a cornerstone in the dissemination of research findings related to the design, synthesis, and development of therapeutic agents. The Journal of Medicinal Chemistry is recognized for its significant impact in the scientific community, as evidenced by its 2022 impact factor of 7.3. This metric reflects the journal's influence and the importance of its content in shaping the future of drug discovery and development. The journal serves as a vital resource for chemists, pharmacologists, and other researchers interested in the molecular mechanisms of drug action and the optimization of therapeutic compounds.
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