Chemokines and Chemokine receptors

Chemokines belong to the large family of chemotactic cytokines. Chemokines are divided by structural similarities into C, CC, CXC, and CXXXC subfamilies, according to the cysteine configuration. Chemokines are small (8-14 kDa) water-soluble proteins, which with their G protein coupled receptors form a complex network that is an important part of the immune system, cell adhesion, cytoskeletal rearrangement, and cell migration. Chemokines participate also in neuronal migration, and at least some chemokines belong to neuropeptides.

At the site of inflammation, white blood cells cells and vascular endothelial cells produce chemokines to recruit certain leukocyte subtypes and regulate the inflammatory response. Neutrophils express abundantly two interleukin-8 receptors, CXCR1 and CXCR2. Chemokine receptors are upregulated on the inflammatory cells in atherosclerotic lesions (Liu et al., 2013). Chemokine receptors are also upregulated in certain tumours, and provide therefore a target for imaging cancer; however, the separation of specific tumour uptake from the uptake in inflammatory cells is not possible.

HIV-1 uses certain chemokine receptors to enter the T cells.


C-X-C chemokine receptor 4 (CXCR4, CD184, fusin) is normally expressed on white blood cells and hematopoietic progenitor cells in the bone marrow. The native ligand of CXCR4 is CXCL12, a 72-amino-acid chemokine. Upregulation of CXCR4 is seen in inflammatory diseases, including arthritis. Upregulation is present also in many cancer types, related to the proliferation of the tumour cells, resistance to chemotherapy, and metastasis.

Radiolabelled peptides targeting CXCR4 have been developed, including [68Ga]NOTA-NFB, [68Ga]pentixafor, Al[18F]NOTA-T140 (Yan et al., 2016), N-[11C]methyl-AMD3465 (Hartimath et al., 2017), and [18F]RPS-544 (Amor-Coarasa et al., 2018).

Atherosclerotic lesions can be detected using [68Ga]pentixafor. Tissue-to-blood ratio (TBR) at large arteries correlates with cardiovascular risk factors, and TBR offers good reproducibility (Li et al., 2018; Weiberg et al., 2018).

Despite the normal uptake in bone marrow, [68Ga]pentixafor is promising tracer for detecting chronic infection of the bone (Bouter et al., 2018). [68Ga]pentixafor may also enable detection of urinary tract infections after kidney transplantation (Derlin et al., 2017).

N-[11C]methyl-AMD3465 could be used to assess drug-induced CXCR4 occupancy in rat tumour model (Hartimath et al., 2017). [68Ga]pentixafor may have potential in assessment of response to therapy in human cancers (Herhaus et al., 2017).


C-C chemokine receptor type 5 (CCR5, CD195) is expressed on T cells, monocytes, macrophages, microglia, eosinophils, and dendritic cells. CCR5 is also expressed on some cancer cells.

Expression of CCR5 in mouse atherosclerosis model has been studied using [64Cu]DOTA-DAPTA-comb nanoparticles (Luehmann et al., 2014).

See also:


Smit MJ, Lira SA, Leurs R (eds.): Chemokine Receptors as Drug Targets. Wiley, 2011.

Tschammer N (ed.): Chemokines - Chemokines and Their Receptors in Drug Discovery. Springer, 2015. doi: 10.1007/978-3-319-14060-5.

Walenkamp AME, Lapa C, Herrmann K, Wester H-J. CXCR4 ligands: the next big hit? J Nucl Med. 2017; 58: 77S-82S. doi: 10.2967/jnumed.116.186874.

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Updated at: 2018-10-11
Created at: 2016-06-04
Written by: Vesa Oikonen