Korean Journal of Radiology

  • 제24권9호
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  • Pages.871-889
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  • 2023
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  • 1229-6929(pISSN)
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  • 2005-8330(eISSN)
대한영상의학회 (The Korean Society of Radiology)
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Research Progress of CXCR4-Targeting Radioligands for Oncologic Imaging

  • Yanzhi Wang (Key Laboratory for Experimental Teratology of the Ministry of Education and Research Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University) ;
  • Feng Gao (Key Laboratory for Experimental Teratology of the Ministry of Education and Research Center for Experimental Nuclear Medicine, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University)
  • 투고 : 2023.01.31
  • 심사 : 2023.07.07
  • 발행 : 2023.09.01
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⟨ 이전 논문 다음 논문 ⟩

초록

C-X-C motif chemokine receptor 4 (CXCR4) plays a key role in various physiological functions, such as immune processes and disease development, and can influence angiogenesis, proliferation, and distant metastasis in tumors. Recently, several radioligands, including peptides, small molecules, and nanoclusters, have been developed to target CXCR4 for diagnostic purposes, thereby providing new diagnostic strategies based on CXCR4. Herein, we focus on the recent research progress of CXCR4-targeting radioligands for tumor diagnosis. We discuss their application in the diagnosis of hematological tumors, such as lymphomas, multiple myelomas, chronic lymphocytic leukemias, and myeloproliferative tumors, as well as nonhematological tumors, including tumors of the esophagus, breast, and central nervous system. Additionally, we explored the theranostic applications of CXCR4-targeting radioligands in tumors. Targeting CXCR4 using nuclear medicine shows promise as a method for tumor diagnosis, and further research is warranted to enhance its clinical applicability.

키워드

과제정보

This work gained great support by core facilities sharing platform of Shandong University.

참고문헌

  1. De Silva RA, Peyre K, Pullambhatla M, Fox JJ, Pomper MG, Nimmagadda S. Imaging CXCR4 expression in human cancer xenografts: evaluation of monocyclam (64)Cu-AMD3465. J Nucl Med 2011;52:986-993 https://doi.org/10.2967/jnumed.110.085613
  2. Weiss ID, Jacobson O, Kiesewetter DO, Jacobus JP, Szajek LP, Chen X, et al. Positron emission tomography imaging of tumors expressing the human chemokine receptor CXCR4 in mice with the use of 64Cu-AMD3100. Mol Imaging Biol 2012;14:106-114 https://doi.org/10.1007/s11307-010-0466-y
  3. Renard I, Domarkas J, Poty S, Burke BP, Roberts DP, Goze C, et al. In vivo validation of (68)Ga-labeled AMD3100 conjugates for PET imaging of CXCR4. Nucl Med Biol 2023;120-121:108335
  4. Muz B, Bandara N, Mpoy C, Sun J, Alhallak K, Azab F, et al. CXCR4-targeted PET imaging using (64)Cu-AMD3100 for detection of Waldenstrom Macroglobulinemia. Cancer Biol Ther 2020;21:52-60
  5. Weiss ID, Huff LM, Evbuomwan MO, Xu X, Dang HD, Velez DS, et al. Screening of cancer tissue arrays identifies CXCR4 on adrenocortical carcinoma: correlates with expression and quantification on metastases using (64)Cu-plerixafor PET. Oncotarget 2017;8:73387-73406 https://doi.org/10.18632/oncotarget.19945
  6. Hartimath SV, Domanska UM, Walenkamp AM, Rudi A J O D, de Vries EF. [(99m)Tc]O(2)-AMD3100 as a SPECT tracer for CXCR4 receptor imaging. Nucl Med Biol 2013;40:507-517 https://doi.org/10.1016/j.nucmedbio.2013.02.003
  7. Jacobson O, Weiss ID, Szajek L, Farber JM, Kiesewetter DO. (64) Cu-AMD3100--a novel imaging agent for targeting chemokine receptor CXCR4. Bioorg Med Chem 2009;17:1486-1493 https://doi.org/10.1016/j.bmc.2009.01.014
  8. Buck AK, Haug A, Dreher N, Lambertini A, Higuchi T, Lapa C et al. Imaging of C-X-C motif chemokine receptor 4 expression in 690 patients with solid or hematologic neoplasms using (68)Ga-pentixafor PET. J Nucl Med 2022;63:1687-1692
  9. Demmer O, Gourni E, Schumacher U, Kessler H, Wester HJ. PET imaging of CXCR4 receptors in cancer by a new optimized ligand. ChemMedChem 2011;10:1789-1791 https://doi.org/10.1002/cmdc.201100320
  10. Gourni E, Demmer O, Schottelius M, D'Alessandria C, Schulz S, Dijkgraaf I, et al. PET of CXCR4 expression by a (68)Ga-labeled highly specific targeted contrast agent. J Nucl Med 2011;52:1803-1810 https://doi.org/10.2967/jnumed.111.098798
  11. Poschenrieder A, Schottelius M, Osl T, Schwaiger M, Wester HJ. [(64)Cu]NOTA-pentixather enables high resolution PET imaging of CXCR4 expression in a preclinical lymphoma model. EJNMMI Radiopharm Chem 2017;2:2
  12. Schottelius M, Osl T, Poschenrieder A, Hoffmann F, Beykan S, Hanscheid H, et al. [(177)Lu]pentixather: comprehensive preclinical characterization of a first CXCR4-directed endoradiotherapeutic agent. Theranostics 2017;7:2350-2362 https://doi.org/10.7150/thno.19119
  13. Chen Z, Xue Q, Yao S. Nuclear medicine application of pentixafor/pentixather targeting CXCR4 for imaging and therapy in related disease. Mini Rev Med Chem 2023;23:787-803
  14. Herrmann K, Schottelius M, Lapa C, Osl T, Poschenrieder A, Hanscheid H, et al. First-in-human experience of CXCR4-directed endoradiotherapy with (177)Lu- and (90)Y-labeled pentixather in advanced-stage multiple myeloma with extensive intra- and extramedullary disease. J Nucl Med 2016;57:248-251 https://doi.org/10.2967/jnumed.115.167361
  15. Jacobson O, Weiss ID, Szajek LP, Niu G, Ma Y, Kiesewetter DO, et al. PET imaging of CXCR4 using copper-64 labeled peptide antagonist. Theranostics 2011;1:251-262 https://doi.org/10.7150/thno/v01p0251
  16. Kwon D, Lozada J, Zhang Z, Zeisler J, Poon R, Zhang C, et al. High-contrast CXCR4-targeted (18)F-PET imaging using a potent and selective antagonist. Mol Pharm 2021;18:187-197 https://doi.org/10.1021/acs.molpharmaceut.0c00785
  17. Luyten K, Van Loy T, Cawthorne C, Deroose CM, Schols D, Bormans G, et al. D-peptide-based probe for CXCR4-targeted molecular imaging and radionuclide therapy. Pharmaceutics 2021;13:1619
  18. Peng T, Wang X, Li Z, Bi L, Gao J, Yang M, et al. Preclinical evaluation of [(64)Cu]NOTA-CP01 as a PET imaging agent for metastatic esophageal squamous cell carcinoma. Mol Pharm 2021;18:3638-3648 https://doi.org/10.1021/acs.molpharmaceut.1c00600
  19. Burke BP, Miranda CS, Lee RE, Renard I, Nigam S, Clemente GS, et al. (64)Cu PET imaging of the CXCR4 chemokine receptor using a cross-bridged cyclam bis-tetraazamacrocyclic antagonist. J Nucl Med 2020;61:123-128 https://doi.org/10.2967/jnumed.118.218008
  20. Brickute D, Braga M, Kaliszczak MA, Barnes C, Lau D, Carroll L, et al. Development and evaluation of an (18)F-Radiolabeled monocyclam derivative for imaging CXCR4 expression. Mol Pharm 2019;16:2106-2117
  21. Suzuki K, Ui T, Nagano A, Hino A, Arano Y. C-terminalmodified LY2510924: a versatile scaffold for targeting C-X-C chemokine receptor type 4. Sci Rep 2019;9:15284
  22. Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, et al. Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 2010;330:1066-1071 https://doi.org/10.1126/science.1194396
  23. Lira SA, Furtado GC. The biology of chemokines and their receptors. Immunol Res 2012;54:111-120 https://doi.org/10.1007/s12026-012-8313-7
  24. Loetscher M, Geiser T, O'Reilly T, Zwahlen R, Baggiolini M, Moser B. Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem 1994;269:232-237 https://doi.org/10.1016/S0021-9258(17)42339-8
  25. Hughes CE, Nibbs R. A guide to chemokines and their receptors. FEBS J 2018;285:2944-2971 https://doi.org/10.1111/febs.14466
  26. Juarez J, Bendall L, Bradstock K. Chemokines and their receptors as therapeutic targets: the role of the SDF-1/CXCR4 axis. Curr Pharm Des 2004;10:1245-1259 https://doi.org/10.2174/1381612043452640
  27. Shim H, Oishi S, Fujii N. Chemokine receptor CXCR4 as a therapeutic target for neuroectodermal tumors. Semin Cancer Biol 2009;19:123-134 https://doi.org/10.1016/j.semcancer.2008.11.004
  28. Zou YR, Kottmann AH, Kuroda M, Taniuchi I, Littman DR. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 1998;393:595-599 https://doi.org/10.1038/31269
  29. Moser B, Loetscher P. Lymphocyte traffic control by chemokines. Nat Immunol 2001;2:123-128 https://doi.org/10.1038/84219
  30. Murphy PM. The molecular biology of leukocyte chemoattractant receptors. Annu Rev Immunol 1994;12:593-633 https://doi.org/10.1146/annurev.iy.12.040194.003113
  31. Cui L, Qu H, Xiao T, Zhao M, Jolkkonen J, Zhao C. Stromal cell-derived factor-1 and its receptor CXCR4 in adult neurogenesis after cerebral ischemia. Restor Neurol Neurosci 2013;31:239-251 https://doi.org/10.3233/RNN-120271
  32. Richardson BE, Lehmann R. Mechanisms guiding primordial germ cell migration: strategies from different organisms. Nat Rev Mol Cell Biol 2010;11:37-49 https://doi.org/10.1038/nrm2815
  33. Agarwal U, Ghalayini W, Dong F, Weber K, Zou YR, Rabbany SY, et al. Role of cardiac myocyte CXCR4 expression in development and left ventricular remodeling after acute myocardial infarction. Circ Res 2010;107:667-676 https://doi.org/10.1161/CIRCRESAHA.110.223289
  34. Sainz J, Sata M. CXCR4, a key modulator of vascular progenitor cells. Arterioscler Thromb Vasc Biol 2007;27:263-265 https://doi.org/10.1161/01.ATV.0000256727.34148.e2
  35. Feng Y, Broder CC, Kennedy PE, Berger EA. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 1996;272:872-877 https://doi.org/10.1126/science.272.5263.872
  36. Nagafuchi Y, Shoda H, Sumitomo S, Nakachi S, Kato R, Tsuchida Y, et al. Immunophenotyping of rheumatoid arthritis reveals a linkage between HLA-DRB1 genotype, CXCR4 expression on memory CD4(+) T cells, and disease activity. Sci Rep 2016;6:29338
  37. Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol 2009;27:165-197 https://doi.org/10.1146/annurev.immunol.021908.132620
  38. Schober A, Bernhagen J, Weber C. Chemokine-like functions of MIF in atherosclerosis. J Mol Med (Berl) 2008;86:761-770 https://doi.org/10.1007/s00109-008-0334-2
  39. Fang HY, Munch NS, Schottelius M, Ingermann J, Liu H, Schauer M, et al. CXCR4 is a potential target for diagnostic PET/CT imaging in barrett's dysplasia and esophageal adenocarcinoma. Clin Cancer Res 2018;24:1048-1061 https://doi.org/10.1158/1078-0432.CCR-17-1756
  40. Baba O, Huang LH, Elvington A, Szpakowska M, Sultan D, Heo GS, et al. CXCR4-binding positron emission tomography tracers link monocyte recruitment and endothelial injury in murine atherosclerosis. Arterioscler Thromb Vasc Biol 2021;41:822-836 https://doi.org/10.1161/ATVBAHA.120.315053
  41. Bonham LW, Karch CM, Fan CC, Tan C, Geier EG, Wang Y, et al. CXCR4 involvement in neurodegenerative diseases. Transl Psychiatry 2018;8:73
  42. Domanska UM, Kruizinga RC, Nagengast WB, Timmer-Bosscha H, Huls G, de Vries EG, et al. A review on CXCR4/CXCL12 axis in oncology: no place to hide. Eur J Cancer 2013;49:219-230 https://doi.org/10.1016/j.ejca.2012.05.005
  43. Burger JA, Kipps TJ. CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment. Blood 2006;107:1761-1767
  44. Williams SA, Harata-Lee Y, Comerford I, Anderson RL, Smyth MJ, McColl SR. Multiple functions of CXCL12 in a syngeneic model of breast cancer. Mol Cancer 2010;9:250
  45. Arya M, Patel HR, McGurk C, Tatoud R, Klocker H, Masters J, et al. The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis. J Exp Ther Oncol 2004;4:291-303
  46. Darash-Yahana M, Pikarsky E, Abramovitch R, Zeira E, Pal B, Karplus R, et al. Role of high expression levels of CXCR4 in tumor growth, vascularization,and metastasis. FASEB J 2004;18:1240-1242 https://doi.org/10.1096/fj.03-0935fje
  47. Su L, Zhang J, Xu H, Wang Y, Chu Y, Liu R, et al. Differential expression of CXCR4 is associated with the metastatic potential of human non-small cell lung cancer cells. Clin Cancer Res 2005;11:8273-8280 https://doi.org/10.1158/1078-0432.CCR-05-0537
  48. Phillips RJ, Burdick MD, Lutz M, Belperio JA, Keane MP, Strieter RM. The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases. Am J Respir Crit Care Med 2003;167:1676-1686 https://doi.org/10.1164/rccm.200301-071OC
  49. Speetjens FM, Liefers GJ, Korbee CJ, Mesker WE, van de Velde CJ, van Vlierberghe RL, et al. Nuclear localization of CXCR4 determines prognosis for colorectal cancer patients. Cancer Microenviron 2009;2:1-7 https://doi.org/10.1007/s12307-008-0016-1
  50. Terasaki M, Sugita Y, Arakawa F, Okada Y, Ohshima K, Shigemori M. CXCL12/CXCR4 signaling in malignant brain tumors: A potential pharmacological therapeutic target. Brain Tumor Pathol 2011;28:89-97 https://doi.org/10.1007/s10014-010-0013-1
  51. Muller A, Homey B, Soto H, Ge N, Catron D, Buchanan ME, et al. Involvement of chemokine receptors in breast cancer metastasis. Nature 2001;410:50-56 https://doi.org/10.1038/35065016
  52. Zlotnik A, Burkhardt AM, Homey B. Homeostatic chemokine receptors and organ-specific metastasis. Nat Rev Immunol 2011;11:597-606 https://doi.org/10.1038/nrc3093
  53. Guo F, Wang Y, Liu J, Mok SC, Xue F, Zhang W. CXCL12/CXCR4: a symbiotic bridge linking cancer cells and their stromal neighbors in oncogenic communication networks. Oncogene 2016;35:816-826 https://doi.org/10.1038/onc.2015.139
  54. Scala S. Molecular pathways: targeting the CXCR4-CXCL12 axis--untapped potential in the tumor microenvironment. Clin Cancer Res 2015;21:4278-4285 https://doi.org/10.1158/1078-0432.CCR-14-0914
  55. Bagri A, Gurney T, He X, Zou YR, Littman DR, Tessier-Lavigne M, et al. The chemokine SDF1 regulates migration of dentate granule cells. Development 2002;129:4249-4260 https://doi.org/10.1242/dev.129.18.4249
  56. Kucia M, Reca R, Miekus K, Wanzeck J, Wojakowski W, Janowska-Wieczorek A, et al. Trafficking of normal stem cells and metastasis of cancer stem cells involve similar mechanisms: pivotal role of the SDF-1-CXCR4 axis. Stem Cells 2005;23:879-894 https://doi.org/10.1634/stemcells.2004-0342
  57. Teicher BA, Fricker SP. CXCL12 (SDF-1)/CXCR4 pathway in cancer. Clin Cancer Res 2010;16:2927-2931 https://doi.org/10.1158/1078-0432.CCR-09-2329
  58. Chatterjee S, Behnam Azad B, Nimmagadda S. The intricate role of CXCR4 in cancer. Adv Cancer Res 2014;124:31-82 https://doi.org/10.1016/B978-0-12-411638-2.00002-1
  59. Sun Y, Cheng Z, Ma L, Pei G. Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J Biol Chem 2002;277:49212-49219
  60. Liebick M, Henze S, Vogt V, Oppermann M. Functional consequences of chemically-induced β-arrestin binding to chemokine receptors CXCR4 and CCR5 in the absence of ligand stimulation. Cell Signal 2017;38:201-211 https://doi.org/10.1016/j.cellsig.2017.07.010
  61. Wang Y, Wang Z, Jia F, Xu Q, Shu Z, Deng J, et al. CXCR4-guided liposomes regulating hypoxic and immunosuppressive microenvironment for sorafenib-resistant tumor treatment. Bioact Mater 2022;17:147-161 https://doi.org/10.1016/j.bioactmat.2022.01.003
  62. Xiao Y, Chen J, Zhou H, Zeng X, Ruan Z, Pu Z, et al. Combining p53 mRNA nanotherapy with immune checkpoint blockade reprograms the immune microenvironment for effective cancer therapy. Nat Commun 2022;13:758
  63. Choueiri TK, Atkins MB, Rose TL, Alter RS, Ju Y, Niland K, et al. A phase 1b trial of the CXCR4 inhibitor mavorixafor and nivolumab in advanced renal cell carcinoma patients with no prior response to nivolumab monotherapy. Invest New Drugs 2021;39:1019-1027 https://doi.org/10.1007/s10637-020-01058-2
  64. Niu J, Huang Y, Zhang L. CXCR4 silencing inhibits invasion and migration of human laryngeal cancer Hep-2 cells. Int J Clin Exp Pathol 2015;8:6255-6261
  65. Wester HJ, Keller U, Schottelius M, Beer A, Philipp-Abbrederis K, Hoffmann F, et al. Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging. Theranostics 2015;5:618-630 https://doi.org/10.7150/thno.11251
  66. Ahn JY, Seo K, Weinberg OK, Arber DA. The prognostic value of CXCR4 in acute myeloid leukemia. Appl Immunohistochem Mol Morphol 2013;21:79-84 https://doi.org/10.1097/PAI.0b013e3182606f4d
  67. Spoo AC, Lubbert M, Wierda WG, Burger JA. CXCR4 is a prognostic marker in acute myelogenous leukemia. Blood 2007;109:786-791
  68. Hiller DJ, Meschonat C, Kim R, Li BD, Chu QD. Chemokine receptor CXCR4 level in primary tumors independently predicts outcome for patients with locally advanced breast cancer. Surgery 2011;150:459-465 https://doi.org/10.1016/j.surg.2011.07.005
  69. Zucca E, Copie-Bergman C, Ricardi U, Thieblemont C, Raderer M, Ladetto M. Gastric marginal zone lymphoma of MALT type: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2013;24 Suppl 6:vi144-vi148 https://doi.org/10.1093/annonc/mdt343
  70. Haug AR, Leisser A, Wadsak W, Mitterhauser M, Pfaff S, Kropf S, et al. Prospective non-invasive evaluation of CXCR4 expression for the diagnosis of MALT lymphoma using [(68) Ga]Ga-pentixafor-PET/MRI. Theranostics 2019;9:3653-3658 https://doi.org/10.7150/thno.31032
  71. Mayerhoefer ME, Raderer M, Lamm W, Pichler V, Pfaff S, Weber M, et al. CXCR4 PET imaging of mantle cell lymphoma using [(68)Ga]Pentixafor: comparison with [(18)F]FDG-PET. Theranostics 2021;11:567-578 https://doi.org/10.7150/thno.48620
  72. Fonseca R, Hayman S. Waldenstrom macroglobulinaemia. Br J Haematol 2007;138:700-720 https://doi.org/10.1111/j.1365-2141.2007.06724.x
  73. Duell J, Krummenast F, Schirbel A, Klassen P, Samnick S, Rauert-Wunderlich H, et al. Improved primary staging of marginal-zone lymphoma by addition of CXCR4-directed PET/CT. J Nucl Med 2021;62:1415-1421 https://doi.org/10.2967/jnumed.120.257279
  74. Pan Q, Cao X, Luo Y, Li J, Feng J, Li F. Chemokine receptor-4 targeted PET/CT with (68)Ga-pentixafor in assessment of newly diagnosed multiple myeloma: comparison to (18)F-FDG PET/CT. Eur J Nucl Med Mol Imaging 2020;47:537-546 https://doi.org/10.1007/s00259-019-04605-z
  75. Walker RC, Brown TL, Jones-Jackson LB, De Blanche L, Bartel T. Imaging of multiple myeloma and related plasma cell dyscrasias. J Nucl Med 2012;53:1091-1101 https://doi.org/10.2967/jnumed.111.098830
  76. Lapa C, Schreder M, Schirbel A, Samnick S, Kortum KM, Herrmann K, et al. [(68)Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma - comparison to [(18)F]FDG and laboratory values. Theranostics 2017;7:205-212 https://doi.org/10.7150/thno.16576
  77. Mayerhoefer ME, Jaeger U, Staber P, Raderer M, Wadsak W, Pfaff S, et al. [(68)Ga]Ga-pentixafor PET/MRI for CXCR4 imaging of chronic lymphocytic leukemia: preliminary results. Invest Radiol 2018;53:403-408 https://doi.org/10.1097/RLI.0000000000000469
  78. Spivak JL. Myeloproliferative neoplasms. N Engl J Med 2017;376:2168-2181 https://doi.org/10.1056/NEJMra1406186
  79. Kraus S, Dierks A, Rasche L, Kertels O, Kircher M, Schirbel A, et al. (68)Ga-pentixafor PET/CT for detection of chemokine receptor CXCR4 expression in myeloproliferative neoplasms. J Nucl Med 2022;63:96-99 https://doi.org/10.2967/jnumed.121.262206
  80. Yang H, Chen YX. Improvement analysis of article quality in World Journal of Gastroenterology during 2008-2012. World J Gastroenterol 2013;19:7830-7835 https://doi.org/10.3748/wjg.v19.i44.7830
  81. Kaifi JT, Yekebas EF, Schurr P, Obonyo D, Wachowiak R, Busch P, et al. Tumor-cell homing to lymph nodes and bone marrow and CXCR4 expression in esophageal cancer. J Natl Cancer Inst 2005;97:1840-1847 https://doi.org/10.1093/jnci/dji431
  82. Wang X, Cao Y, Zhang S, Chen Z, Fan L, Shen X, et al. Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer. Oncotarget 2017;8:36149-36160 https://doi.org/10.18632/oncotarget.15254
  83. Zhang M, Zhang L, Cui M, Ye W, Zhang P, Zhou S, et al. miR302b inhibits cancer-related inflammation by targeting ERBB4, IRF2 and CXCR4 in esophageal cancer. Oncotarget 2017;8:49053-49063 https://doi.org/10.18632/oncotarget.17041
  84. Linde P, Baues C, Wegen S, Trommer M, Quaas A, Rosenbrock J, et al. Pentixafor PET/CT for imaging of chemokine receptor 4 expression in esophageal cancer - a first clinical approach. Cancer Imaging 2021;21:22
  85. Grueneisen J, Nagarajah J, Buchbender C, Hoffmann O, Schaarschmidt BM, Poeppel T, et al. Positron emission tomography/magnetic resonance imaging for local tumor staging in patients with primary breast cancer: a comparison with positron emission Tomography/Computed tomography and magnetic resonance imaging. Invest Radiol 2015;50:505-513 https://doi.org/10.1097/RLI.0000000000000197
  86. Garcia-Velloso MJ, Ribelles MJ, Rodriguez M, Fernandez-Montero A, Sancho L, Prieto E, et al. MRI fused with prone FDG PET/CT improves the primary tumour staging of patients with breast cancer. Eur Radiol 2017;27:3190-3198 https://doi.org/10.1007/s00330-016-4685-8
  87. Liang X, Yu J, Wen B, Xie J, Cai Q, Yang Q. MRI and FDG-PET/CT based assessment of axillary lymph node metastasis in early breast cancer: a meta-analysis. Clin Radiol 2017;72:295-301 https://doi.org/10.1016/j.crad.2016.12.001
  88. Weiss ID, Jacobson O. Molecular imaging of chemokine receptor CXCR4. Theranostics 2013;3:76-84 https://doi.org/10.7150/thno.4835
  89. Philipp-Abbrederis K, Herrmann K, Knop S, Schottelius M, Eiber M, Luckerath K, et al. In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma. EMBO Mol Med 2015;7:477-487 https://doi.org/10.15252/emmm.201404698
  90. George GP, Pisaneschi F, Stevens E, Nguyen QD, Aberg O, Spivey AC, et al. Scavenging strategy for specific activity improvement: application to a new CXCR4-specific cyclopentapeptide positron emission tomography tracer. J Labelled Comp Radiopharm 2013;56:679-685 https://doi.org/10.1002/jlcr.3095
  91. Smith MC, Luker KE, Garbow JR, Prior JL, Jackson E, Piwnica-Worms D, et al. CXCR4 regulates growth of both primary and metastatic breast cancer. Cancer Res 2004;64:8604-8612 https://doi.org/10.1158/0008-5472.CAN-04-1844
  92. Vag T, Steiger K, Rossmann A, Keller U, Noske A, Herhaus P, et al. PET imaging of chemokine receptor CXCR4 in patients with primary and recurrent breast carcinoma. EJNMMI Res 2018;8:90
  93. Nagarsheth N, Wicha MS, Zou W. Chemokines in the cancer microenvironment and their relevance in cancer immunotherapy. Nat Rev Immunol 2017;17:559-572 https://doi.org/10.1038/nri.2017.49
  94. Fu P, Tian L, Cao X, Li L, Xu P, Zhao C. Imaging CXCR4 expression with (99m)Tc-radiolabeled small-interference RNA in experimental human breast cancer xenografts. Mol Imaging Biol 2016;18:353-359
  95. Zhao Y, Detering L, Sultan D, Cooper ML, You M, Cho S, et al. Gold nanoclusters doped with (64)Cu for CXCR4 positron emission tomography imaging of breast cancer and metastasis. ACS Nano 2016;10:5959-5970 https://doi.org/10.1021/acsnano.6b01326
  96. Li H, Zhang X, Wu HY, Sun L, Ma Y, Xu J, et al. (64)Cu-labeled ubiquitin for PET imaging of CXCR4 expression in mouse breast tumor. ACS Omega 2019;4:12432-12437 https://doi.org/10.1021/acsomega.9b00678
  97. Demoin DW, Shindo M, Zhang H, Edwards KJ, Serganova I, Pillarsetty NV, et al. Synthesis and evaluation of an (18) F-labeled pyrimidine-pyridine amine for targeting CXCR4 receptors in gliomas. Nucl Med Biol 2016;43:606-611 https://doi.org/10.1016/j.nucmedbio.2016.05.005
  98. Chiang GC, Kovanlikaya I, Choi C, Ramakrishna R, Magge R, Shungu DC. Magnetic resonance spectroscopy, positron emission tomography and radiogenomics-relevance to glioma. Front Neurol 2018;9:33
  99. Galldiks N, Lohmann P, Albert NL, Tonn JC, Langen KJ. Current status of PET imaging in neuro-oncology. Neurooncol Adv 2019;1:vdz010
  100. Hutterer M, Nowosielski M, Putzer D, Jansen NL, Seiz M, Schocke M, et al. [(18)F]-fluoro-ethyl-L-tyrosine PET: a valuable diagnostic tool in neuro-oncology, but not all that glitters is glioma. Neuro Oncol 2013;15:341-351 https://doi.org/10.1093/neuonc/nos300
  101. Hartimath SV, van Waarde A, Dierckx RA, de Vries EF. Evaluation of N-[(11)C]Methyl-AMD3465 as a PET tracer for imaging of CXCR4 receptor expression in a C6 glioma tumor model. Mol Pharm 2014;11:3810-3817 https://doi.org/10.1021/mp500398r
  102. Zhang H, Maeda M, Shindo M, Ko M, Mane M, Grommes C, et al. Imaging CXCR4 expression with iodinated and brominated cyclam derivatives. Mol Imaging Biol 2020;22:1184-1196 https://doi.org/10.1007/s11307-020-01480-1
  103. Jacobs SM, Wesseling P, de Keizer B, Tolboom N, Ververs F, Krijger GC, et al. CXCR4 expression in glioblastoma tissue and the potential for PET imaging and treatment with [(68) Ga]Ga-pentixafor /[(177)Lu]Lu-pentixather. Eur J Nucl Med Mol Imaging 2022;49:481-491 https://doi.org/10.1007/s00259-021-05196-4
  104. Shiels MS, Pfeiffer RM, Besson C, Clarke CA, Morton LM, Nogueira L, et al. Trends in primary central nervous system lymphoma incidence and survival in the U.S. Br J Haematol 2016;174:417-424 https://doi.org/10.1111/bjh.14073
  105. Mendez JS, Ostrom QT, Gittleman H, Kruchko C, DeAngelis LM, Barnholtz-Sloan JS, et al. The elderly left behind-changes in survival trends of primary central nervous system lymphoma over the past 4 decades. Neuro Oncol 2018;20:687-694 https://doi.org/10.1093/neuonc/nox187
  106. Villano JL, Koshy M, Shaikh H, Dolecek TA, McCarthy BJ. Age, gender, and racial differences in incidence and survival in primary CNS lymphoma. Br J Cancer 2011;105:1414-1418 https://doi.org/10.1038/bjc.2011.357
  107. Herhaus P, Lipkova J, Lammer F, Yakushev I, Vag T, Slotta-Huspenina J, et al. CXCR4-targeted PET imaging of central nervous system B-Cell lymphoma. J Nucl Med 2020;61:1765-1771 https://doi.org/10.2967/jnumed.120.241703
  108. Boehme V, Zeynalova S, Kloess M, Loeffler M, Kaiser U, Pfreundschuh M, et al. Incidence and risk factors of central nervous system recurrence in aggressive lymphoma--a survey of 1693 patients treated in protocols of the German High-Grade Non-Hodgkin's Lymphoma Study Group (DSHNHL). Ann Oncol 2007;18:149-157 https://doi.org/10.1093/annonc/mdl327
  109. Deckert M, Engert A, Bruck W, Ferreri AJ, Finke J, Illerhaus G, et al. Modern concepts in the biology, diagnosis, differential diagnosis and treatment of primary central nervous system lymphoma. Leukemia 2011;25:1797-1807 https://doi.org/10.1038/leu.2011.169
  110. Korfel A, Schlegel U. Diagnosis and treatment of primary CNS lymphoma. Nat Rev Neurol 2013;9:317-327 https://doi.org/10.1038/nrneurol.2013.83
  111. Doolittle ND, Abrey LE, Shenkier TN, Tali S, Bromberg JE, Neuwelt EA, et al. Brain parenchyma involvement as isolated central nervous system relapse of systemic non-Hodgkin lymphoma: an International Primary CNS Lymphoma Collaborative Group report. Blood 2008;111:1085-1093 https://doi.org/10.1182/blood-2007-07-101402
  112. Dreyling M, Campo E, Hermine O, Jerkeman M, Le Gouill S, Rule S, et al. Newly diagnosed and relapsed mantle cell lymphoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2017;28(suppl 4):iv62-iv71 https://doi.org/10.1093/annonc/mdx223
  113. Toh CH, Castillo M, Wong AM, Wei KC, Wong HF, Ng SH, et al. Primary cerebral lymphoma and glioblastoma multiforme: differences in diffusion characteristics evaluated with diffusion tensor imaging. AJNR Am J Neuroradiol 2008;29:471-475 https://doi.org/10.3174/ajnr.A0872
  114. Abrey LE, Batchelor TT, Ferreri AJ, Gospodarowicz M, Pulczynski EJ, Zucca E, et al. Report of an international workshop to standardize baseline evaluation and response criteria for primary CNS lymphoma. J Clin Oncol 2005;23:5034-5043 https://doi.org/10.1200/JCO.2005.13.524
  115. Nabavizadeh SA, Vossough A, Hajmomenian M, Assadsangabi R, Mohan S. Neuroimaging in central nervous system lymphoma. Hematol Oncol Clin North Am 2016;30:799-821 https://doi.org/10.1016/j.hoc.2016.03.005
  116. Baraniskin A, Deckert M, Schulte-Altedorneburg G, Schlegel U, Schroers R. Current strategies in the diagnosis of diffuse large B-cell lymphoma of the central nervous system. Br J Haematol 2012;156:421-432 https://doi.org/10.1111/j.1365-2141.2011.08928.x
  117. Starzer AM, Berghoff AS, Traub-Weidinger T, Haug AR, Widhalm G, Hacker M, et al. Assessment of central nervous system lymphoma based on CXCR4 expression in vivo using (68)Ga-pentixafor PET/MRI. Clin Nucl Med 2021;46:16-20 https://doi.org/10.1097/RLU.0000000000003404
  118. Stemmer-Rachamimov AO, Louis DN, Nielsen GP, Antonescu CR, Borowsky AD, Bronson RT, et al. Comparative pathology of nerve sheath tumors in mouse models and humans. Cancer Res 2004;64:3718-3724 https://doi.org/10.1158/0008-5472.CAN-03-4079
  119. Breun M, Monoranu CM, Kessler AF, Matthies C, Lohr M, Hagemann C, et al. [(68)Ga]-pentixafor PET/CT for CXCR4-mediated imaging of vestibular schwannomas. Front Oncol 2019;9:503
  120. Lapa C, Herrmann K, Schirbel A, Hanscheid H, Luckerath K, Schottelius M, et al. CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed multiple myeloma. Theranostics 2017;7:1589-1597 https://doi.org/10.7150/thno.19050