Theranostic applications of CXCR4-targeted imaging ligands in lymphoma: integrating diagnosis and precision therapy.

IF 1.8 Q3 RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING

American journal of nuclear medicine and molecular imaging Pub Date : 2026-02-15 eCollection Date: 2026-01-01 DOI:10.62347/RXPV2461

Karena R Dhamecha, Owen C Booth, Oluwaseyi M Oderinde, Qi-Huang Zheng

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引用次数: 0

Abstract

C-X-C chemokine receptor 4 (CXCR4) is a G protein-coupled receptor implicated in immune regulation, tumor progression, and therapy resistance. In lymphoma, CXCR4 overexpression promotes malignant cell survival via microenvironmental retention and activation of pro-survival pathways, correlating with poor prognosis. Its extracellular localization makes it a strong candidate for selective molecular imaging and targeted therapy. This review summarizes recent advances in CXCR4-targeted agents for lymphoma. Peptide-based radiotracers (⁶⁸Ga-Pentixafor, [¹⁸F]AlF-NOTA-QHY-04, [⁶⁸Ga]Ga-BL02) and small molecules ([⁶⁴Cu]AMD3100, [¹⁸F]MCFB) offer high specificity and favorable pharmacokinetics for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging. Therapeutic strategies include peptide antagonists (BL-8040, Balixafortide), radioligand therapies ([¹⁷⁷Lu]Pentixather, [¹⁷⁷Lu]Lu-BL02), small-molecule inhibitors (Plerixafor, WK1), and monoclonal antibodies (PF-06747143, Ulocuplomab, LY2624587). These approaches have demonstrated efficacy in reducing tumor burden and enhancing chemosensitivity. Key challenges include off-target uptake due to physiological CXCR4 expression and compensatory signaling via CXCR7. Future directions involve dual-receptor targeting, nanoparticle-based delivery, and integration into precision oncology for both hematologic and solid tumors.

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cxcr4靶向成像配体在淋巴瘤中的应用：综合诊断与精准治疗

C-X-C趋化因子受体4 （CXCR4）是一种G蛋白偶联受体，与免疫调节、肿瘤进展和治疗耐药性有关。在淋巴瘤中，CXCR4过表达通过微环境保留和促生存通路的激活促进恶性细胞存活，与不良预后相关。它的细胞外定位使其成为选择性分子成像和靶向治疗的有力候选者。本文综述了近年来cxcr4靶向淋巴瘤药物的研究进展。基于肽的放射性示踪剂（68Ga- pentixafor, [18F] alf - nota - qhy04, [68Ga]Ga-BL02）和小分子（[64Cu]AMD3100, [18F]MCFB）为正电子发射断层扫描（PET）和单光子发射计算机断层扫描（SPECT）成像提供了高特异性和良好的药代动力学。治疗策略包括肽拮抗剂（BL-8040, Balixafortide），放射配位药物（[177Lu]Pentixather, [177Lu]Lu-BL02），小分子抑制剂（Plerixafor, WK1）和单克隆抗体（PF-06747143, ulocplomab, LY2624587）。这些方法在减轻肿瘤负荷和提高化疗敏感性方面已被证明有效。主要的挑战包括由于生理上CXCR4的表达和通过CXCR7的代偿信号传导导致的脱靶摄取。未来的方向包括双受体靶向，基于纳米颗粒的递送，以及整合到血液和实体肿瘤的精确肿瘤学中。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

American journal of nuclear medicine and molecular imaging RADIOLOGY, NUCLEAR MEDICINE & MEDICAL IMAGING-

自引率

4.00%

发文量

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.