Leung Kam
National Center for Biotechnology Information, NLM, NIH, Bethesda, MD
Chemokine receptors are G-protein–coupled receptors directing cell movement toward higher concentrations of chemokines. Chemokine receptor 4 (CXCR4) and its ligand, stromal cell–derived factor-1 (SDF-1 or CXCL12), are known to play a major role in the migration of progenitor cells during embryonic development of the central nervous, cardiovascular, and hematopoietic systems (1, 2). In addition, this CXCR4-SDF-1 receptor system has a function in the development, progression, and spread of various cancers (3), and the CXCR4 acts as a co-receptor for human immunodeficiency virus (HIV) on CD4 T cells (4). It has also been suggested that CXCR4/SDF-1 interaction participates in the pathogenesis of neurodegenerative and inflammatory conditions (5). CXCR4 is expressed by many different types of cancers, and overexpression of CXCR4 in cancers indicates poor prognosis with aggressive and metastatic tumors and resistance to chemotherapy (6). CXCR4 is considered to play an important role in HIV infections and cancers. It is critical to perform imaging studies to measure CXCR4 levels under conditions for various pathological and physiological conditions (7). Tc-SDF-1 has been used with single-photon emission computed tomography (SPECT) to determine changes in CXCR4 expression in the heart after a myocardial infarction. Cu-1,1’-[1,4-Phenylenebis(methylene)]-bis[1,4,8,11-tetraaza-cyclotetradecane] (Cu-AMD3100), an inhibitor of CXCR4 activity, has been studied with positron emission tomography (PET) (8). An In-labeled CXCR4 antagonist peptide, In-Ac-TZ14011, has been developed for SPECT imaging of CXCR4 expression in xenograft tumors in mice (9). Tamamura et al. (10) identified a 14-amino-acid peptide (T140, Arg-Arg-Natl-Cys-Tyr-Cit-Lys-d-Lys-Pro-Tyr-Arg-Cit-Cys-Arg-NH) with high anti-HIV and CXCR4 antagonistic activities . Jacobson et al. (11) radiolabeled T140 with 4-[F]fluorobenzoic acid ([F]FBA) to form 4-[F]fluorobenzoyl-Arg-Arg-Natl-Cys-Tyr-Cit-Lys-d-Lys-Pro-Tyr-Arg-Cit-Cys-Arg-NH (4-[F]F-T140) for PET imaging of tumor CXCR4 expression with a high tumor/background ratio.
趋化因子受体是G蛋白偶联受体，可引导细胞向趋化因子浓度更高的方向移动。已知趋化因子受体4（CXCR4）及其配体基质细胞衍生因子-1（SDF-1或CXCL12）在中枢神经、心血管和造血系统胚胎发育过程中祖细胞的迁移中起主要作用（1,2）。此外，这种CXCR4-SDF-1受体系统在各种癌症的发生、发展和扩散中发挥作用（3），并且CXCR4在CD4 T细胞上作为人类免疫缺陷病毒（HIV）的共受体发挥作用（4）。也有人提出CXCR4/SDF-1相互作用参与神经退行性疾病和炎症性疾病的发病机制（5）。CXCR4在许多不同类型的癌症中表达，癌症中CXCR4的过表达表明预后不良，肿瘤具有侵袭性和转移性，并且对化疗耐药（6）。CXCR4被认为在HIV感染和癌症中起重要作用。在各种病理和生理条件下进行成像研究以测量CXCR4水平至关重要（7）。锝标记的SDF-1已与单光子发射计算机断层扫描（SPECT）一起用于确定心肌梗死后心脏中CXCR4表达的变化。CXCR4活性抑制剂铜-1,1'-[1,4-亚苯基双（亚甲基）]-双[1,4,8,11-四氮杂环十四烷]（铜-AMD3100）已通过正电子发射断层扫描（PET）进行研究（8）。一种铟标记的CXCR4拮抗剂肽铟-Ac-TZ14011已被开发用于小鼠异种移植肿瘤中CXCR4表达的SPECT成像（9）。田村等人（10）鉴定出一种具有高抗HIV和CXCR4拮抗活性的14氨基酸肽（T140，精氨酸-精氨酸-Natl-半胱氨酸-酪氨酸-瓜氨酸-赖氨酸-d-赖氨酸-脯氨酸-酪氨酸-精氨酸-瓜氨酸-半胱氨酸-精氨酸-NH）。雅各布森等人（11）用4-[F]氟苯甲酸（[F]FBA）对T140进行放射性标记，以形成4-[F]氟苯甲酰-精氨酸-精氨酸-Natl-半胱氨酸-酪氨酸-瓜氨酸-赖氨酸-d-赖氨酸-脯氨酸-酪氨酸-精氨酸-瓜氨酸-半胱氨酸-精氨酸-NH（4-[F]F-T140），用于肿瘤CXCR4表达的PET成像，肿瘤/背景比值高。
