Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Jun 12;28(12):4707.
doi: 10.3390/molecules28124707.

CXCR4-Targeted Radiopharmaceuticals for the Imaging and Therapy of Malignant Tumors

Jingjing Yu  1   2 , Xu Zhou  1 , Langtao Shen  1   3
Affiliations
Review

CXCR4-Targeted Radiopharmaceuticals for the Imaging and Therapy of Malignant Tumors

Jingjing Yu et al. Molecules. .

Abstract

C-X-C chemokine receptor type 4 (CXCR4), also known as fusin or CD184, is a 7-transmembrane helix G-protein-coupled receptor that is encoded by the CXCR4 gene. Involved in various physiological processes, CXCR4 could form an interaction with its endogenous partner, chemokine ligand 12 (CXCL12), which is also named SDF-1. In the past several decades, the CXCR4/CXCL12 couple has attracted a large amount of research interest due to its critical functions in the occurrence and development of refractory diseases, such as HIV infection, inflammatory diseases, and metastatic cancer, including breast cancer, gastric cancer, and non-small cell lung cancer. Furthermore, overexpression of CXCR4 in tumor tissues was shown to have a high correlation with tumor aggressiveness and elevated risks of metastasis and recurrence. The pivotal roles of CXCR4 have encouraged an effort around the world to investigate CXCR4-targeted imaging and therapeutics. In this review, we would like to summarize the implementation of CXCR4-targeted radiopharmaceuticals in the field of various kinds of carcinomas. The nomenclature, structure, properties, and functions of chemokines and chemokine receptors are briefly introduced. Radiopharmaceuticals that could target CXCR4 will be described in detail according to their structure, such as pentapeptide-based structures, heptapeptide-based structures, nonapeptide-based structures, etc. To make this review a comprehensive and informative article, we would also like to provide the predictive prospects for the CXCR4-targeted species in future clinical development.

Keywords: CXCL12; CXCR4; chemokine receptor; metastatic cancer; radiopharmaceuticals.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic diagram of CXCR4.
Figure 2
Figure 2
Structures of AMD3100, CB-Bicyclam, and AMD3465.
Figure 3
Figure 3
Structures of 76Br-HZ270-1, RAD1-24, RAD1-52, [18F]RPS-544, [18F]RPS-534, [18F]RPS-547, and [18F]MCFB.
Figure 4
Figure 4
Structures of CPCR4-2 (Pentixafor), NOTA-pentixather, and NODA-NCS-pentixather.
Figure 5
Figure 5
Structures of [125I]CPCR4.3, DOTA-r-a-ABA-CPCR4, DOTA-r-a-ABA-iodoCPCR4, 99mTc-CXCR4-L, 177Lu-CXCR4-L, and MK007.
Figure 6
Figure 6
Structures of heptapeptide-based molecule-1, heptapeptide-based molecule-2, FRM001, BL01, BL08, BL09, and NOTA-CP01.
Figure 7
Figure 7
PET/CT and PET alone maximal intensity projections of [68Ga]Ga-BL01 at 1 and 2 h postinjection in mice bearing Daudi Burkitt’s lymphoma xenografts. The blocking study was performed by injection of LY2510924 15 min before tracer administration. The scale bar is in units of %ID/g from 0 to 1.2 × 10 (t = tumor; l = liver; k = kidney; bl = bladder). Reprinted with permission from [70]. Copyright © 2019 American Chemical Society.
Figure 8
Figure 8
Maximum intensity projections for PET/CT and PET alone at 1 h p.i., 2 h p.i., and 1 h p.i., blocking (A) [18F]BL08, (B) [18F]BL09, and (C) [68Ga]Ga-Pentixafor. The blocking was performed via injection of LY2510924 15 min prior. The scales of the PET images of [18F]BL08 and [18F]BL09 are 0–9% ID/g, and the scale of the PET images of [68Ga]Ga-Pentixafor is 0–6% ID/g. Reprinted with permission from [71]. Copyright © 2021 American Chemical Society.
Figure 9
Figure 9
Structures of DOTA-AMD3100, NODAGA-AMD3100, and NODAGA-ph-AMD3100.
Figure 10
Figure 10
Structures of [18F]RPS-510, [18F]MSX-122F, and [18F]benzenesulfonamide-based molecule-1.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Bianchi M.E., Mezzapelle R. The chemokine receptor CXCR4 in cell proliferation and tissue regeneration. Front. Immunol. 2020;11:2109. doi: 10.3389/fimmu.2020.02109. - DOI - PMC - PubMed
    1. Hughes C.E., Nibbs R.J.B. A guide to chemokines and their receptors. FEBS J. 2018;285:2944–2971. doi: 10.1111/febs.14466. - DOI - PMC - PubMed
    1. Horuk R. Chemokine receptors. Cytokine Growth Factor Rev. 2001;12:313–335. doi: 10.1016/S1359-6101(01)00014-4. - DOI - PubMed
    1. Crijns H., Vanheule V., Proost P. Targeting chemokine—Glycosaminoglycan interactions to inhibit inflammation. Front. Immunol. 2020;11:483. doi: 10.3389/fimmu.2020.00483. - DOI - PMC - PubMed
    1. Fakhari A., Aghanejad A., Jalilian A.R., Gharepapagh E. Recent developments in targeted imaging of CXCR4-chemokine receptor. J. Radioanal. Nucl. Chem. 2018;317:1–14. doi: 10.1007/s10967-018-5910-5. - DOI

Grants and funding

This research received no external funding.