Henan Joint International Research Laboratory of Living Polymerizations and Functional Nanomaterials, Henan Key Laboratory of Advanced Nylon Materials and Application, School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450001, China.
Department of Nuclear Medicine, Henan Key Laboratory of Novel Molecular Probes and Clinical Translation in Nuclear Medicine, Henan Provincial People's Hospital & the People's Hospital of Zhengzhou University, Zhengzhou 450003, China.
Bioconjug Chem. 2024 May 15;35(5):567-574. doi: 10.1021/acs.bioconjchem.4c00167. Epub 2024 Apr 18.
The exploration of pharmaceutically active agents and positron emission tomography (PET) tracers targeting CXCR4 has been a focal point in cancer research given its pivotal role in the development and progression of various cancers. While significant strides have been made in PET imaging with radiometal-labeled tracers, the landscape of F-labeled small molecule tracers remains relatively limited. Herein, we introduce a novel and promising derivative, [F]SFB-AMD3465, as a targeted PET tracer for CXCR4. The compound was synthesized by modifying the pyridine ring of AMD3465, which was subsequently labeled with F using [F]SFB. The study provides comprehensive insights into the design, synthesis, and biological evaluation of [F]SFB-AMD3465. and assessments demonstrated the CXCR4-dependent, specific, and sensitive uptake of [F]SFB-AMD3465 in the CXCR4-overexpressing 4T1 cell line and the corresponding xenograft-bearing mouse model. These findings contribute to bridging the gap in F-labeled PET tracers for CXCR4 and underscore the potential of [F]SFB-AMD3465 as a PET radiotracer for CXCR4 imaging.
探索针对 CXCR4 的药物活性化合物和正电子发射断层扫描 (PET) 示踪剂一直是癌症研究的重点，因为它在各种癌症的发展和进展中起着关键作用。虽然使用放射性金属标记示踪剂在 PET 成像方面取得了重大进展，但 F 标记小分子示踪剂的领域仍然相对有限。在此，我们介绍了一种新型且有前途的衍生物 [F]SFB-AMD3465，作为 CXCR4 的靶向 PET 示踪剂。该化合物通过修饰 AMD3465 的吡啶环合成，随后使用 [F]SFB 对其进行 F 标记。该研究提供了对 [F]SFB-AMD3465 的设计、合成和生物学评估的全面了解。评估表明，[F]SFB-AMD3465 在 CXCR4 过表达的 4T1 细胞系和相应的荷瘤小鼠模型中表现出 CXCR4 依赖性、特异性和敏感性摄取。这些发现有助于缩小 F 标记的 CXCR4 PET 示踪剂之间的差距，并强调了 [F]SFB-AMD3465 作为 CXCR4 成像的 PET 放射性示踪剂的潜力。
