A radioactive and fluorescent dual modality cysteine cathepsin-B activity-based probe for the detection and treatment evaluation in rheumatoid arthritis.

IF 2 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING
American journal of nuclear medicine and molecular imaging Pub Date : 2024-08-25 eCollection Date: 2024-01-01 DOI:10.62347/IAED6442
Honghui Guo, Yanjing Chen, Lianbo Zhou, Xin Xiang, Feng He, Xingdou Chen, Wenjie Fu, Yu Long, Yunhua Wang, Xiaowei Ma
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引用次数: 0

Abstract

Activated macrophages are key effector cells and specific markers in patients with rheumatoid arthritis (RA). Cysteine cathepsin B (CTS-B) is highly expressed in macrophages and positively associated with RA activity and severity. This study aims to evaluate an activity-based multi-modality diagnostic agent, 68Ga-BMX2, which targets CTS-B to visualize the arthritis activity and evaluate the treatment efficacy. A CTS-B activity-based probe, BMX2, was labeled efficiently with 68Ga to produce 68Ga-BMX2 for fluorescent and positron emission tomography (PET) multi-modality imaging. The affinity and specificity of BMX2 binding with the CTS-B enzyme in macrophages were determined by radioactive experiment using RAW 264.7 cell lines, with CA074 and BMX5 as the inhibitors to test the specificity of the binding. Then, PET and fluorescence imaging were acquired on collagen-induced arthritis (CIA) mice. Additionally, the treatment monitoring capability of 68Ga-BMX2 PET/CT imaging was tested with methotrexate (MTX). RAW 264.7 macrophage cells showed significant uptake of 68Ga-BMX2. The binding of BMX2 with CTS-B in RAW 264.7 macrophage cells is time-dependent and could be blocked by CA074 and BMX5. In vivo optical and PET imaging showed high signals in the right hind arthritis in CIA mice from 68Ga-BMX2 and BMX2 accumulated for at least 120 h. Additionally, 68Ga-BMX2 signals were significantly reduced in the MTX-treated CIA mice compared to the control group. The 68Ga-BMX2, a radioactive and fluorescent dual-modality diagnostic agent targeting CTS-B, demonstrated a practical approach for CIA PET and fluorescence imaging. The 68Ga-BMX2 multimodality imaging could significantly monitor the treatment response in the CIA mice.

基于半胱氨酸酪蛋白酶-B 活性的放射性和荧光双模式探针,用于类风湿性关节炎的检测和治疗评估。
活化的巨噬细胞是类风湿性关节炎(RA)患者的关键效应细胞和特异性标志物。半胱氨酸酪蛋白酶 B(CTS-B)在巨噬细胞中高度表达,与 RA 的活性和严重程度呈正相关。本研究旨在评估一种以CTS-B为靶点的基于活性的多模态诊断试剂68Ga-BMX2,以观察关节炎的活动性并评估治疗效果。一种基于 CTS-B 活性的探针 BMX2 被 68Ga 高效标记,生成 68Ga-BMX2 用于荧光和正电子发射断层扫描(PET)多模态成像。以 RAW 264.7 细胞系为研究对象,通过放射性实验测定了 BMX2 与巨噬细胞中 CTS-B 酶结合的亲和力和特异性,并以 CA074 和 BMX5 作为抑制剂测试了结合的特异性。然后,对胶原诱导的关节炎(CIA)小鼠进行 PET 和荧光成像。此外,还测试了 68Ga-BMX2 PET/CT 成像与甲氨蝶呤(MTX)的治疗监测能力。RAW 264.7 巨噬细胞显示出对 68Ga-BMX2 的显著摄取。在 RAW 264.7 巨噬细胞中,BMX2 与 CTS-B 的结合具有时间依赖性,并可被 CA074 和 BMX5 阻断。体内光学和 PET 成像显示,68Ga-BMX2 和 BMX2 在 CIA 小鼠右后关节炎中的高信号累积至少 120 小时。68Ga-BMX2是一种针对CTS-B的放射性和荧光双模态诊断剂,为CIA PET和荧光成像提供了一种实用的方法。68Ga-BMX2 多模态成像可显著监测 CIA 小鼠的治疗反应。
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来源期刊
American journal of nuclear medicine and molecular imaging
American journal of nuclear medicine and molecular imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-
自引率
4.00%
发文量
4
期刊介绍: The scope of AJNMMI encompasses all areas of molecular imaging, including but not limited to: positron emission tomography (PET), single-photon emission computed tomography (SPECT), molecular magnetic resonance imaging, magnetic resonance spectroscopy, optical bioluminescence, optical fluorescence, targeted ultrasound, photoacoustic imaging, etc. AJNMMI welcomes original and review articles on both clinical investigation and preclinical research. Occasionally, special topic issues, short communications, editorials, and invited perspectives will also be published. Manuscripts, including figures and tables, must be original and not under consideration by another journal.
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