PIPELINE

PentixaPharm is proceeding its development pipeline in lymphoma located in the central nervous system in an advanced diagnostic trial with the PET-based agent PentixaFor as well as an early phase therapeutic trial with the targeted radiotherapy agent PentixaTher.

PentixaFor, a small peptide based [68Ga]Gallium PET imaging agent, addresses specifically the chemokine 4 receptor, expressed by a multitude of malignant diseases in oncological, cardiovascular and inflammatory indications allowing for personalised molecular imaging with high specificity and sensitivity.

PentixaTher, the complementary therapeutic agent to PentixaFor, equipped with the high energy beta emitter [90Y]Yttrium targets oncological malignancies via internal peptide receptor radioligand therapy.

The lead development for PentixaFor and PentixaTher focuses on hematological indications targeting unmet medical needs for patients and offers benefits over existing therapies via a reduced side effect profile.

LITERATURE

Buck, A. K., Stolzenburg, A., Hänscheid, H., Schirbel, A., Lückerath, K., Schottelius, M., Wester, H.-J., & Lapa, C. (2017). Chemokine receptor—Directed imaging and therapy. Methods (San Diego, Calif.), 130, 63–71. https://doi.org/10.1016/j.ymeth.2017.09.002

Eiber, M., Kratochwil, C., Lapa, C., & Brenner, W. (2021). Nuklearmedizinische Theranostik. Der Onkologe. https://doi.org/10.1007/s00761-021-00956-1

Herrmann, K., Schwaiger, M., Lewis, J. S., Solomon, S. B., McNeil, B. J., Baumann, M., Gambhir, S. S., Hricak, H., & Weissleder, R. (2020). Radiotheranostics: A roadmap for future development. The Lancet Oncology, 21(3), e146–e156. https://doi.org/10.1016/S1470-2045(19)30821-6

Jamet, B., Bailly, C., Carlier, T., Touzeau, C., Nanni, C., Zamagni, E., Barré, L., Michaud, A.-V., Chérel, M., Moreau, P., Bodet-Milin, C., & Kraeber-Bodéré, F. (2019). Interest of Pet Imaging in Multiple Myeloma. Frontiers in Medicine, 6, 69. https://doi.org/10.3389/fmed.2019.00069

Kircher, M., Herhaus, P., Schottelius, M., Buck, A. K., Werner, R. A., Wester, H.-J., Keller, U., & Lapa, C. (2018). CXCR4-directed theranostics in oncology and inflammation. Annals of Nuclear Medicine, 32(8), 503–511. https://doi.org/10.1007/s12149-018-1290-8

Mayerhoefer, M. E., Archibald, S. J., Messiou, C., Staudenherz, A., Berzaczy, D., & Schöder, H. (2020). MRI and PET/MRI in hematologic malignancies. Journal of Magnetic Resonance Imaging, 51(5), 1325–1335. https://doi.org/10.1002/jmri.26848

Mesguich, C., Zanotti-Fregonara, P., & Hindié, E. (2016). New Perspectives Offered by Nuclear Medicine for the Imaging and Therapy of Multiple Myeloma. Theranostics, 6(2), 287–290. https://doi.org/10.7150/thno.14400

Narula, J., Dilsizian, V., & Chandrashekhar, Y. (2015). Molecular Imaging: From Deep Pearl Diving to Enlightenment. JACC. Cardiovascular Imaging, 8(12), 1472–1474. https://doi.org/10.1016/j.jcmg.2015.11.004

Pandit-Taskar, N. (2018). Functional Imaging Methods for Assessment of Minimal Residual Disease in Multiple Myeloma: Current Status and Novel ImmunoPET Based Methods. Seminars in Hematology, 55(1), 22–32. https://doi.org/10.1053/j.seminhematol.2018.02.009

Toczek, J., & Riou, L. (2020). Considerations on PET/MR imaging of carotid plaque inflammation with 68Ga-Pentixafor. Journal of Nuclear Cardiology. https://doi.org/10.1007/s12350-020-02354-3

Walenkamp, A. M. E., Lapa, C., Herrmann, K., & Wester, H.-J. (2017). CXCR4 Ligands: The Next Big Hit? Journal of Nuclear Medicine, 58(Supplement 2), 77S-82S. https://doi.org/10.2967/jnumed.116.186874

Preclinical

Demmer, O., Dijkgraaf, I., Schumacher, U., Marinelli, L., Cosconati, S., Gourni, E., Wester, H.-J., & Kessler, H. (2011). Design, synthesis, and functionalization of dimeric peptides targeting chemokine receptor CXCR4. Journal of Medicinal Chemistry, 54(21), 7648–7662. https://doi.org/10.1021/jm2009716

Demmer, O., Gourni, E., Schumacher, U., Kessler, H., & Wester, H.-J. (2011). PET imaging of CXCR4 receptors in cancer by a new optimized ligand. ChemMedChem, 6(10), 1789–1791. https://doi.org/10.1002/cmdc.201100320

Derlin, T., Sedding, D. G., Dutzmann, J., Haghikia, A., König, T., Napp, L. C., Schütze, C., Owsianski-Hille, N., Wester, H.-J., Kropf, S., Thackeray, J. T., Bankstahl, J. P., Geworski, L., Ross, T. L., Bauersachs, J., & Bengel, F. M. (2018). Imaging of chemokine receptor CXCR4 expression in culprit and nonculprit coronary atherosclerotic plaque using motion-corrected [68Ga]pentixafor PET/CT. European Journal of Nuclear Medicine and Molecular Imaging, 45(11), 1934–1944. https://doi.org/10.1007/s00259-018-4076-2

Grosse, G. M., Bascuñana, P., Schulz-Schaeffer, W. J., Teebken, O. E., Wilhelmi, M., Worthmann, H., Ross, T. L., Wester, H.-J., Kropf, S., Derlin, T., Bengel, F. M., Bankstahl, J. P., & Weissenborn, K. (2018). Targeting Chemokine Receptor CXCR4 and Translocator Protein for Characterization of High-Risk Plaque in Carotid Stenosis Ex Vivo. Stroke, 49(8), 1988–1991. https://doi.org/10.1161/STROKEAHA.118.021070

Gourni, E., Demmer, O., Schottelius, M., D’Alessandria, C., Schulz, S., Dijkgraaf, I., Schumacher, U., Schwaiger, M., Kessler, H., & Wester, H.-J. (2011). PET of CXCR4 expression by a (68)Ga-labeled highly specific targeted contrast agent. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 52(11), 1803–1810. https://doi.org/10.2967/jnumed.111.098798

Habringer, S., Lapa, C., Herhaus, P., Schottelius, M., Istvanffy, R., Steiger, K., Slotta-Huspenina, J., Schirbel, A., Hänscheid, H., Kircher, S., Buck, A. K., Götze, K., Vick, B., Jeremias, I., Schwaiger, M., Peschel, C., Oostendorp, R., Wester, H.-J., Grigoleit, G.-U., & Keller, U. (2018). Dual Targeting of Acute Leukemia and Supporting Niche by CXCR4-Directed Theranostics. Theranostics, 8(2), 369–383. https://doi.org/10.7150/thno.21397

Herhaus, P., Habringer, S., Vag, T., Steiger, K., Slotta-Huspenina, J., Gerngroß, C., Wiestler, B., Wester, H.-J., Schwaiger, M., & Keller, U. (2017). Response assessment with the CXCR4-directed positron emission tomography tracer [68Ga]Pentixafor in a patient with extranodal marginal zone lymphoma of the orbital cavities. EJNMMI Research, 7(1), 51. https://doi.org/10.1186/s13550-017-0294-z

Herrmann, K., Lapa, C., Wester, H.-J., Schottelius, M., Schiepers, C., Eberlein, U., Bluemel, C., Keller, U., Knop, S., Kropf, S., Schirbel, A., Buck, A. K., & Lassmann, M. (2015). Biodistribution and radiation dosimetry for the chemokine receptor CXCR4-targeting probe 68Ga-pentixafor. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 56(3), 410–416. https://doi.org/10.2967/jnumed.114.151647

Hyafil, F., Pelisek, J., Laitinen, I., Schottelius, M., Mohring, M., Döring, Y., van der Vorst, E. P. C., Kallmayer, M., Steiger, K., Poschenrieder, A., Notni, J., Fischer, J., Baumgartner, C., Rischpler, C., Nekolla, S. G., Weber, C., Eckstein, H.-H., Wester, H.-J., & Schwaiger, M. (2017). Imaging the Cytokine Receptor CXCR4 in Atherosclerotic Plaques with the Radiotracer 68Ga-Pentixafor for PET. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 58(3), 499–506. https://doi.org/10.2967/jnumed.116.179663

Liu, D., Li, M., Bellizzi, A., Menda, Y., Lee, D., Nourmahnad, K., Ghobrial, S., Schultz, M., & ODorisio, M. S. (2018). Preclinical evaluation of CXCR4 as novel radio-theranostic target for high grade neuroendocrine and neuroblastoma tumors. Journal of Nuclear Medicine, 59(supplement 1), 1313–1313.

Martin, R., Jüttler, S., Müller, M., & Wester, H.-J. (2014). Cationic eluate pretreatment for automated synthesis of [⁶⁸Ga]CPCR4.2. Nuclear Medicine and Biology, 41(1), 84–89. https://doi.org/10.1016/j.nucmedbio.2013.09.002

Meester, E. J., de Blois, E., Krenning, B. J., van der Steen, A. F. W., Norenberg, J. P., van Gaalen, K., Bernsen, M. R., de Jong, M., & van der Heiden, K. (2021). Autoradiographical assessment of inflammation-targeting radioligands for atherosclerosis imaging: Potential for plaque phenotype identification. EJNMMI Research, 11(1), 27. https://doi.org/10.1186/s13550-021-00772-z

Philipp-Abbrederis, K., Herrmann, K., Knop, S., Schottelius, M., Eiber, M., Lückerath, K., Pietschmann, E., Habringer, S., Gerngroß, C., Franke, K., Rudelius, M., Schirbel, A., Lapa, C., Schwamborn, K., Steidle, S., Hartmann, E., Rosenwald, A., Kropf, S., Beer, A. J., … Keller, U. (2015). In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma. EMBO Molecular Medicine, 7(4), 477–487. https://doi.org/10.15252/emmm.201404698

Poschenrieder, A., Osl, T., Schottelius, M., Hoffmann, F., Wirtz, M., Schwaiger, M., & Wester, H.-J. (2016). First 18F-Labeled Pentixafor-Based Imaging Agent for PET Imaging of CXCR4 Expression In Vivo. Tomography (Ann Arbor, Mich.), 2(2), 85–93. https://doi.org/10.18383/j.tom.2016.00130

Poschenrieder, A., Schottelius, M., Schwaiger, M., Kessler, H., & Wester, H.-J. (2016). The influence of different metal-chelate conjugates of pentixafor on the CXCR4 affinity. EJNMMI Research, 6(1), 36. https://doi.org/10.1186/s13550-016-0193-8

Poschenrieder, A., Schottelius, M., Schwaiger, M., & Wester, H.-J. (2016). Preclinical evaluation of [(68)Ga]NOTA-pentixafor for PET imaging of CXCR4 expression in vivo—A comparison to [(68)Ga]pentixafor. EJNMMI Research, 6(1), 70. https://doi.org/10.1186/s13550-016-0227-2

Schwarzenböck, S. M., Stenzel, J., Otto, T., Helldorff, H. V., Bergner, C., Kurth, J., Polei, S., Lindner, T., Rauer, R., Hohn, A., Hakenberg, O. W., Wester, H. J., Vollmar, B., & Krause, B. J. (2017). [68Ga]pentixafor for CXCR4 imaging in a PC-3 prostate cancer xenograft model—Comparison with [18F]FDG PET/CT, MRI and ex vivo receptor expression. Oncotarget, 8(56), 95606–95619. https://doi.org/10.18632/oncotarget.21024

Spreckelmeyer, S., Schulze, O., & Brenner, W. (2020). Fully-automated production of [68Ga]Ga-PentixaFor on the module Modular Lab-PharmTracer. EJNMMI Radiopharmacy and Chemistry, 5. https://doi.org/10.1186/s41181-020-0091-2

Wester, H. J., Keller, U., Schottelius, M., Beer, A., Philipp-Abbrederis, K., Hoffmann, F., Šimeček, J., Gerngross, C., Lassmann, M., Herrmann, K., Pellegata, N., Rudelius, M., Kessler, H., & Schwaiger, M. (2015). Disclosing the CXCR4 expression in lymphoproliferative diseases by targeted molecular imaging. Theranostics, 5(6), 618–630. https://doi.org/10.7150/thno.11251

Oncology

Bluemel, C., Hahner, S., Heinze, B., Fassnacht, M., Kroiss, M., Bley, T. A., Wester, H.-J., Kropf, S., Lapa, C., Schirbel, A., Buck, A. K., & Herrmann, K. (2017). Investigating the Chemokine Receptor 4 as Potential Theranostic Target in Adrenocortical Cancer Patients. Clinical Nuclear Medicine, 42(1), e29–e34. https://doi.org/10.1097/RLU.0000000000001435

Breun, M., Monoranu, C. M., Kessler, A. F., Matthies, C., Löhr, M., Hagemann, C., Schirbel, A., Rowe, S. P., Pomper, M. G., Buck, A. K., Wester, H.-J., Ernestus, R.-I., & Lapa, C. (2019). [68Ga]-Pentixafor PET/CT for CXCR4-Mediated Imaging of Vestibular Schwannomas. Frontiers in Oncology, 9, 503. https://doi.org/10.3389/fonc.2019.00503

Cui, Y., Zhang, Y., Ding, J., Wang, H., Ma, X., Wang, O., Chang, X., Sun, H., Huo, L., & Tong, A. (2019). A Rare Aldosterone-Producing Adenoma Detected by 68Ga-pentixafor PET-CT: A Case Report and Literature Review. Frontiers in Endocrinology, 10, 810. https://doi.org/10.3389/fendo.2019.00810

Derlin, T., Jonigk, D., Bauersachs, J., & Bengel, F. M. (2016). Molecular Imaging of Chemokine Receptor CXCR4 in Non-Small Cell Lung Cancer Using 68Ga-Pentixafor PET/CT: Comparison With 18F-FDG. Clinical Nuclear Medicine, 41(4), e204-205. https://doi.org/10.1097/RLU.0000000000001092

Ding, J., Tong, A., Zhang, Y., Wen, J., & Huo, L. (2020). Intense 68Ga-Pentixafor Activity in Aldosterone-Producing Adrenal Adenomas. Clinical Nuclear Medicine, 45(4), 336–339. https://doi.org/10.1097/RLU.0000000000002946

Ding, J., Zhang, Y., Wen, J., Zhang, H., Wang, H., Luo, Y., Pan, Q., Zhu, W., Wang, X., Yao, S., Kreissl, M. C., Hacker, M., Tong, A., Huo, L., & Li, X. (2020). Imaging CXCR4 expression in patients with suspected primary hyperaldosteronism. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-020-04722-0

Duell, J., Krummenast, F., Schirbel, A., Klassen, P., Samnick, S., Rauert-Wunderlich, H., Rasche, L., Buck, A. K., Wester, H.-J., Rosenwald, A., Einsele, H., Topp, M. S., Lapa, C., & Kircher, M. (2021). Improved primary staging of marginal zone lymphoma by addition of CXCR4-directed PET/CT. Journal of Nuclear Medicine. https://doi.org/10.2967/jnumed.120.257279

Fang, H.-Y., Münch, N. S., Schottelius, M., Ingermann, J., Liu, H., Schauer, M., Stangl, S., Multhoff, G., Steiger, K., Gerngroß, C., Jesinghaus, M., Weichert, W., Kühl, A. A., Sepulveda, A. R., Wester, H.-J., Wang, T. C., & Quante, M. (2018). CXCR4 Is a Potential Target for Diagnostic PET/CT Imaging in Barrett’s Dysplasia and Esophageal Adenocarcinoma. Clinical Cancer Research, 24(5), 1048–1061. https://doi.org/10.1158/1078-0432.CCR-17-1756

Haug, A. R., Leisser, A., Wadsak, W., Mitterhauser, M., Pfaff, S., Kropf, S., Wester, H.-J., Hacker, M., Hartenbach, M., Kiesewetter-Wiederkehr, B., Raderer, M., & Mayerhoefer, M. E. (2019). Prospective non-invasive evaluation of CXCR4 expression for the diagnosis of MALT lymphoma using [68Ga]Ga-Pentixafor-PET/MRI. Theranostics, 9(12), 3653–3658. https://doi.org/10.7150/thno.31032

Heinze, B., Fuss, C. T., Mulatero, P., Beuschlein, F., Reincke, M., Mustafa, M., Schirbel, A., Deutschbein, T., Williams, T. A., Rhayem, Y., Quinkler, M., Rayes, N., Monticone, S., Wild, V., Gomez-Sanchez, C. E., Reis, A.-C., Petersenn, S., Wester, H.-J., Kropf, S., … Hahner, S. (2018). Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma. Hypertension (Dallas, Tex.: 1979), 71(2), 317–325. https://doi.org/10.1161/HYPERTENSIONAHA.117.09975

Herhaus, P., Habringer, S., Philipp-Abbrederis, K., Vag, T., Gerngross, C., Schottelius, M., Slotta-Huspenina, J., Steiger, K., Altmann, T., Weißer, T., Steidle, S., Schick, M., Jacobs, L., Slawska, J., Müller-Thomas, C., Verbeek, M., Subklewe, M., Peschel, C., Wester, H.-J., … Keller, U. (2016). Targeted positron emission tomography imaging of CXCR4 expression in patients with acute myeloid leukemia. Haematologica, 101(8), 932–940. https://doi.org/10.3324/haematol.2016.142976

Herhaus, P., Habringer, S., Vag, T., Steiger, K., Slotta-Huspenina, J., Gerngroß, C., Wiestler, B., Wester, H.-J., Schwaiger, M., & Keller, U. (2017). Response assessment with the CXCR4-directed positron emission tomography tracer [68Ga]Pentixafor in a patient with extranodal marginal zone lymphoma of the orbital cavities. EJNMMI Research, 7(1), 51. https://doi.org/10.1186/s13550-017-0294-z

Herhaus, P., Lipkova, J., Lammer, F., Yakushev, I., Vag, T., Slotta-Huspenina, J., Habringer, S., Lapa, C., Pukrop, T., Hellwig, D., Wiestler, B., Buck, A. K., Deckert, M., Wester, H.-J., Bassermann, F., Schwaiger, M., Weber, W. A., Menze, B., & Keller, U. (2020). CXCR4-targeted positron emission tomography imaging of central nervous system B-cell lymphoma. Journal of Nuclear Medicine, jnumed.120.241703. https://doi.org/10.2967/jnumed.120.241703

Kraus, S., Dierks, A., Rasche, L., Kertels, O., Kircher, M., Schirbel, A., Zovko, J., Steinbrunn, T., Tibes, R., Wester, H.-J., Buck, A. K., Einsele, H., Kortüm, K. M., Rosenwald, A., & Lapa, C. (2021). 68Ga-Pentixafor-PET/CT imaging represents a novel approach to detect chemokine receptor CXCR4 expression in myeloproliferative neoplasms. Journal of Nuclear Medicine. https://doi.org/10.2967/jnumed.121.262206

Kuyumcu, S., Yilmaz, E., Büyükkaya, F., Özkan, Z. G., & Ünal, S. N. (2018). Imaging of Chemokine Receptor CXCR4 in Mycosis Fungoides Using 68Ga-Pentixafor PET/CT. Clinical Nuclear Medicine, 43(8), 606–608. https://doi.org/10.1097/RLU.0000000000002166

Lapa, C., Kircher, S., Schirbel, A., Rosenwald, A., Kropf, S., Pelzer, T., Walles, T., Buck, A. K., Weber, W. A., Wester, H.-J., Herrmann, K., & Lückerath, K. (2017). Targeting CXCR4 with [68Ga]Pentixafor: A suitable theranostic approach in pleural mesothelioma? Oncotarget, 8(57), 96732–96737. https://doi.org/10.18632/oncotarget.18235

Lapa, C., Lückerath, K., Kleinlein, I., Monoranu, C. M., Linsenmann, T., Kessler, A. F., Rudelius, M., Kropf, S., Buck, A. K., Ernestus, R.-I., Wester, H.-J., Löhr, M., & Herrmann, K. (2016). (68)Ga-Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression in Glioblastoma. Theranostics, 6(3), 428–434. https://doi.org/10.7150/thno.13986

Lapa, C., Lückerath, K., Rudelius, M., Schmid, J.-S., Schoene, A., Schirbel, A., Samnick, S., Pelzer, T., Buck, A. K., Kropf, S., Wester, H.-J., & Herrmann, K. (2016). [68Ga]Pentixafor-PET/CT for imaging of chemokine receptor 4 expression in small cell lung cancer—Initial experience. Oncotarget, 7(8), 9288–9295. https://doi.org/10.18632/oncotarget.7063

Lapa, C., Schreder, M., Schirbel, A., Samnick, S., Kortüm, K. M., Herrmann, K., Kropf, S., Einsele, H., Buck, A. K., Wester, H.-J., Knop, S., & Lückerath, K. (2017). [68Ga]Pentixafor-PET/CT for imaging of chemokine receptor CXCR4 expression in multiple myeloma—Comparison to [18F]FDG and laboratory values. Theranostics, 7(1), 205–212. https://doi.org/10.7150/thno.16576

Linde, P., Baues, C., Wegen, S., Trommer, M., Quaas, A., Rosenbrock, J., Celik, E., Marnitz, S., Bruns, C. J., Fischer, T., Schomaecker, K., Wester, H.-J., Drzezga, A., van Heek, L., & Kobe, C. (2021). Pentixafor PET/CT for imaging of chemokine receptor 4 expression in esophageal cancer – a first clinical approach. Cancer Imaging, 21. https://doi.org/10.1186/s40644-021-00391-w

Lüke, F., Blazquez, R., Yamaci, R. F., Lu, X., Pregler, B., Hannus, S., Menhart, K., Hellwig, D., Wester, H.-J., Kropf, S., Heudobler, D., Grosse, J., Moosbauer, J., Hutterer, M., Hau, P., Riemenschneider, M. J., Bayerlová, M., Bleckmann, A., Polzer, B., … Pukrop, T. (2018). Isolated metastasis of an EGFR-L858R-mutated NSCLC of the meninges: The potential impact of CXCL12/CXCR4 axis in EGFRmut NSCLC in diagnosis, follow-up and treatment. Oncotarget, 9(27), 18844–18857. https://doi.org/10.18632/oncotarget.24787

Luo, Y., Cao, X., Pan, Q., Li, J., Feng, J., & Li, F. (2019). 68Ga-pentixafor PET/CT for imaging of chemokine receptor-4 expression in Waldenström macroglobulinemia/lymphoplasmacytic lymphoma: Comparison to 18F-FDG PET/CT. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine. https://doi.org/10.2967/jnumed.119.226134

Luo, Y., Pan, Q., Feng, J., Cao, X., & Li, F. (2018). Chemokine Receptor CXCR4-Targeted PET/CT With 68Ga-Pentixafor Shows Superiority to 18F-FDG in a Patient With Waldenström Macroglobulinemia. Clinical Nuclear Medicine, 43(7), 548–550. https://doi.org/10.1097/RLU.0000000000002131

Mayerhoefer, M. E., Jaeger, U., Staber, P., Raderer, M., Wadsak, W., Pfaff, S., Kornauth, C., Senn, D., Weber, M., Wester, H.-J., Skrabs, C., & Haug, A. (2018). [68Ga]Ga-Pentixafor PET/MRI for CXCR4 Imaging of Chronic Lymphocytic Leukemia: Preliminary Results. Investigative Radiology, 53(7), 403–408. https://doi.org/10.1097/RLI.0000000000000469

Mayerhoefer, M. E., Raderer, M., Lamm, W., Pichler, V., Pfaff, S., Weber, M., Kiesewetter, B., Hacker, M., Kazianka, L., Staber, P. B., Wester, H.-J., Rohrbeck, J., Simonitsch-Klupp, I., & Haug, A. (2021). CXCR4 PET imaging of mantle cell lymphoma using [68Ga]Pentixafor: Comparison with [18F]FDG-PET. Theranostics, 11(2), 567–578. https://doi.org/10.7150/thno.48620

Pan, Q., Cao, X., Luo, Y., Li, J., Feng, J., & Li, F. (2019). Chemokine receptor-4 targeted PET/CT with 68Ga-Pentixafor in assessment of newly diagnosed multiple myeloma: Comparison to 18F-FDG PET/CT. European Journal of Nuclear Medicine and Molecular Imaging. https://doi.org/10.1007/s00259-019-04605-z

Pan, Q., Luo, Y., Cao, X., Li, J., & Li, F. (2020). Posttreated POEMS Syndrome With Concurrent Follicular Lymphoma Revealed by 18F-FDG and 68Ga-Pentixafor PET/CT. Clinical Nuclear Medicine, 45(3), 220–222. https://doi.org/10.1097/RLU.0000000000002923

Pan, Q., Luo, Y., Cao, X., Ma, Y., & Li, F. (2018). Multiple Myeloma Presenting as a Superscan on 68Ga-Pentixafor PET/CT. Clinical Nuclear Medicine, 43(6), 462–463. https://doi.org/10.1097/RLU.0000000000002067

Pan, Q., Luo, Y., Zhang, Y., Chang, L., Li, J., Cao, X., Li, J., & Li, F. (2020). Preliminary evidence of imaging of chemokine receptor-4-targeted PET/CT with [68Ga]pentixafor in non-Hodgkin lymphoma: Comparison to [18F]FDG. EJNMMI Research, 10. https://doi.org/10.1186/s13550-020-00681-7

Philipp-Abbrederis, K., Herrmann, K., Knop, S., Schottelius, M., Eiber, M., Lückerath, K., Pietschmann, E., Habringer, S., Gerngroß, C., Franke, K., Rudelius, M., Schirbel, A., Lapa, C., Schwamborn, K., Steidle, S., Hartmann, E., Rosenwald, A., Kropf, S., Beer, A. J., … Keller, U. (2015). In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma. EMBO Molecular Medicine, 7(4), 477–487. https://doi.org/10.15252/emmm.201404698

Vag, T., Gerngross, C., Herhaus, P., Eiber, M., Philipp-Abbrederis, K., Graner, F.-P., Ettl, J., Keller, U., Wester, H.-J., & Schwaiger, M. (2016). First Experience with Chemokine Receptor CXCR4-Targeted PET Imaging of Patients with Solid Cancers. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 57(5), 741–746. https://doi.org/10.2967/jnumed.115.161034

Vag, T., Steiger, K., Rossmann, A., Keller, U., Noske, A., Herhaus, P., Ettl, J., Niemeyer, M., Wester, H.-J., & Schwaiger, M. (2018). PET imaging of chemokine receptor CXCR4 in patients with primary and recurrent breast carcinoma. EJNMMI Research, 8(1), 90. https://doi.org/10.1186/s13550-018-0442-0

Watts, A., Singh, B., Basher, R., Singh, H., Bal, A., Kapoor, R., Arora, S. K., Wester, H. J., Mittal, B. R., & Behera, D. (2017). 68Ga-Pentixafor PET/CT demonstrating higher CXCR4 density in small cell lung carcinoma than in non-small cell variant. European Journal of Nuclear Medicine and Molecular Imaging, 44(5), 909–910. https://doi.org/10.1007/s00259-017-3622-7

Weich, A., Werner, R. A., Buck, A. K., Hartrampf, P. E., Serfling, S. E., Scheurlen, M., Wester, H.-J., Meining, A., Kircher, S., Higuchi, T., Pomper, M. G., Rowe, S. P., Lapa, C., & Kircher, M. (2021). CXCR4-Directed PET/CT in Patients with Newly Diagnosed Neuroendocrine Carcinomas. Diagnostics, 11(4). https://doi.org/10.3390/diagnostics11040605

Werner, R. A., Kircher, S., Higuchi, T., Kircher, M., Schirbel, A., Wester, H.-J., Buck, A. K., Pomper, M. G., Rowe, S. P., & Lapa, C. (2019). CXCR4-Directed Imaging in Solid Tumors. Frontiers in Oncology, 9, 770. https://doi.org/10.3389/fonc.2019.00770

Werner, R. A., Weich, A., Higuchi, T., Schmid, J. S., Schirbel, A., Lassmann, M., Wild, V., Rudelius, M., Kudlich, T., Herrmann, K., Scheurlen, M., Buck, A. K., Kropf, S., Wester, H.-J., & Lapa, C. (2017). Imaging of Chemokine Receptor 4 Expression in Neuroendocrine Tumors—A Triple Tracer Comparative Approach. Theranostics, 7(6), 1489–1498. https://doi.org/10.7150/thno.18754

Werner, R. A., Weich, A., Schirbel, A., Samnick, S., Buck, A. K., Higuchi, T., Wester, H.-J., & Lapa, C. (2017). Intraindividual tumor heterogeneity in NET - Further insight by C-X-C motif chemokine receptor 4-directed imaging. European Journal of Nuclear Medicine and Molecular Imaging, 44(3), 553–554. https://doi.org/10.1007/s00259-016-3566-3

Zhou, X., Dierks, A., Kertels, O., Kircher, M., Schirbel, A., Samnick, S., Buck, A. K., Knorz, S., Böckle, D., Scheller, L., Messerschmidt, J., Barakat, M., Kortüm, K. M., Rasche, L., Einsele, H., & Lapa, C. (2020). 18F-FDG, 11C-Methionine, and 68Ga-Pentixafor PET/CT in Patients with Smoldering Multiple Myeloma: Imaging Pattern and Clinical Features. Cancers, 12(8). https://doi.org/10.3390/cancers12082333

Cardiovascular

Derlin, T., Sedding, D. G., Dutzmann, J., Haghikia, A., König, T., Napp, L. C., Schütze, C., Owsianski-Hille, N., Wester, H.-J., Kropf, S., Thackeray, J. T., Bankstahl, J. P., Geworski, L., Ross, T. L., Bauersachs, J., & Bengel, F. M. (2018). Imaging of chemokine receptor CXCR4 expression in culprit and nonculprit coronary atherosclerotic plaque using motion-corrected [68Ga]pentixafor PET/CT. European Journal of Nuclear Medicine and Molecular Imaging, 45(11), 1934–1944. https://doi.org/10.1007/s00259-018-4076-2

Kircher, M., Tran-Gia, J., Kemmer, L., Zhang, X., Schirbel, A., Werner, R. A., Buck, A. K., Wester, H.-J., Hacker, M., Lapa, C., & Li, X. (2020). Imaging Inflammation in Atherosclerosis with CXCR4-Directed 68Ga-Pentixafor PET/CT: Correlation with 18F-FDG PET/CT. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 61(5), 751–756. https://doi.org/10.2967/jnumed.119.234484

Lapa, C., Reiter, T., Werner, R. A., Ertl, G., Wester, H.-J., Buck, A. K., Bauer, W. R., & Herrmann, K. (2015). [(68)Ga]Pentixafor-PET/CT for Imaging of Chemokine Receptor 4 Expression After Myocardial Infarction. JACC. Cardiovascular Imaging, 8(12), 1466–1468. https://doi.org/10.1016/j.jcmg.2015.09.007

Lawal, I. O., Popoola, G. O., Mahapane, J., Kaufmann, J., Davis, C., Ndlovu, H., Maserumule, L. C., Mokoala, K. M. G., Bouterfa, H., Wester, H.-J., Zeevaart, J. R., & Sathekge, M. M. (2020). [68Ga]Ga-Pentixafor for PET Imaging of Vascular Expression of CXCR-4 as a Marker of Arterial Inflammation in HIV-Infected Patients: A Comparison with 18F[FDG] PET Imaging. Biomolecules, 10(12), 1629. https://doi.org/10.3390/biom10121629

Li, X., Heber, D., Leike, T., Beitzke, D., Lu, X., Zhang, X., Wei, Y., Mitterhauser, M., Wadsak, W., Kropf, S., Wester, H. J., Loewe, C., Hacker, M., & Haug, A. R. (2018). [68Ga]Pentixafor-PET/MRI for the detection of Chemokine receptor 4 expression in atherosclerotic plaques. European Journal of Nuclear Medicine and Molecular Imaging, 45(4), 558–566. https://doi.org/10.1007/s00259-017-3831-0

Li, X., Yu, W., Wollenweber, T., Lu, X., Wei, Y., Beitzke, D., Wadsak, W., Kropf, S., Wester, H. J., Haug, A. R., Zhang, X., & Hacker, M. (2019). [68Ga]Pentixafor PET/MR imaging of chemokine receptor 4 expression in the human carotid artery. European Journal of Nuclear Medicine and Molecular Imaging, 46(8), 1616–1625. https://doi.org/10.1007/s00259-019-04322-7

Rausch, I., Beitzke, D., Li, Xiang., Pfaff, S., Rasul, S., Haug, A. R., Mayerhoefer, M. E., Hacker, M., Beyer, T., & Cal-González, J. (2020). Accuracy of PET quantification in [68Ga]Ga-pentixafor PET/MR imaging of carotid plaques. Journal of Nuclear Cardiology. https://doi.org/10.1007/s12350-020-02257-3

Reiter, T., Kircher, M., Schirbel, A., Werner, R. A., Kropf, S., Ertl, G., Buck, A. K., Wester, H.-J., Bauer, W. R., & Lapa, C. (2018). Imaging of C-X-C Motif Chemokine Receptor CXCR4 Expression After Myocardial Infarction With [68Ga]Pentixafor-PET/CT in Correlation With Cardiac MRI. JACC. Cardiovascular Imaging, 11(10), 1541–1543. https://doi.org/10.1016/j.jcmg.2018.01.001

Rischpler, C., Nekolla, S. G., Kossmann, H., Dirschinger, R. J., Schottelius, M., Hyafil, F., Wester, H. J., Laugwitz, K. L., & Schwaiger, M. (2016). Upregulated myocardial CXCR4-expression after myocardial infarction assessed by simultaneous GA-68 pentixafor PET/MRI. Journal of Nuclear Cardiology: Official Publication of the American Society of Nuclear Cardiology, 23(1), 131–133. https://doi.org/10.1007/s12350-015-0347-5

Schmid, J. S., Schirbel, A., Buck, A. K., Kropf, S., Wester, H.-J., & Lapa, C. (2016). [68Ga]Pentixafor-Positron Emission Tomography/Computed Tomography Detects Chemokine Receptor CXCR4 Expression After Ischemic Stroke. Circulation. Cardiovascular Imaging, 9(9), e005217. https://doi.org/10.1161/CIRCIMAGING.116.005217

Thackeray, J. T., Derlin, T., Haghikia, A., Napp, L. C., Wang, Y., Ross, T. L., Schäfer, A., Tillmanns, J., Wester, H. J., Wollert, K. C., Bauersachs, J., & Bengel, F. M. (2015). Molecular Imaging of the Chemokine Receptor CXCR4 After Acute Myocardial Infarction. JACC. Cardiovascular Imaging, 8(12), 1417–1426. https://doi.org/10.1016/j.jcmg.2015.09.008

Weiberg, D., Thackeray, J. T., Daum, G., Sohns, J. M., Kropf, S., Wester, H.-J., Ross, T. L., Bengel, F. M., & Derlin, T. (2018). Clinical Molecular Imaging of Chemokine Receptor CXCR4 Expression in Atherosclerotic Plaque Using 68Ga-Pentixafor PET: Correlation with Cardiovascular Risk Factors and Calcified Plaque Burden. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 59(2), 266–272. https://doi.org/10.2967/jnumed.117.196485

Inflammatory

Bouter, C., Meller, B., Sahlmann, C. O., Staab, W., Wester, H. J., Kropf, S., & Meller, J. (2018). 68Ga-Pentixafor PET/CT Imaging of Chemokine Receptor CXCR4 in Chronic Infection of the Bone: First Insights. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 59(2), 320–326. https://doi.org/10.2967/jnumed.117.193854

Bouter, Y., Meller, B., Sahlmann, C. O., Wolf, B. J., Langer, L., Bankstahl, J. P., Wester, H. J., Kropf, S., Meller, J., & Bouter, C. (2018). Immunohistochemical detection of chemokine receptor 4 expression in chronic osteomyelitis confirms specific uptake in 68Ga-Pentixafor-PET/CT. Nuklearmedizin. Nuclear Medicine, 57(5), 198–203. https://doi.org/10.3413/Nukmed-0971-18-04

Cytawa, W., Kircher, S., Schirbel, A., Shirai, T., Fukushima, K., Buck, A. K., Wester, H.-J., & Lapa, C. (2018). Chemokine Receptor 4 Expression in Primary Sjögren’s Syndrome. Clinical Nuclear Medicine, 43(11), 835–836. https://doi.org/10.1097/RLU.0000000000002258

Derlin, T., Gueler, F., Bräsen, J. H., Schmitz, J., Hartung, D., Herrmann, T. R., Ross, T. L., Wacker, F., Wester, H.-J., Hiss, M., Haller, H., Bengel, F. M., & Hueper, K. (2017). Integrating MRI and Chemokine Receptor CXCR4-Targeted PET for Detection of Leukocyte Infiltration in Complicated Urinary Tract Infections After Kidney Transplantation. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 58(11), 1831–1837. https://doi.org/10.2967/jnumed.117.193037

Derlin, T., Wester, H.-J., Bengel, F. M., & Hueper, K. (2017). Visualization of Posttraumatic Splenosis on Chemokine Receptor CXCR4-Targeted PET/CT. Clinical Nuclear Medicine, 42(6), e317–e318. https://doi.org/10.1097/RLU.0000000000001590

Pan, Q., Luo, Y., Cao, X., Li, J., & Li, F. (2020). Pulmonary Cryptococcosis Accidentally Detected by 68Ga-Pentixafor PET/CT in a Patient With Multiple Myeloma. Clinical Nuclear Medicine, 45(5), 423–425. https://doi.org/10.1097/RLU.0000000000003004

Preclinical

Habringer, S., Lapa, C., Herhaus, P., Schottelius, M., Istvanffy, R., Steiger, K., Slotta-Huspenina, J., Schirbel, A., Hänscheid, H., Kircher, S., Buck, A. K., Götze, K., Vick, B., Jeremias, I., Schwaiger, M., Peschel, C., Oostendorp, R., Wester, H.-J., Grigoleit, G.-U., & Keller, U. (2018). Dual Targeting of Acute Leukemia and Supporting Niche by CXCR4-Directed Theranostics. Theranostics, 8(2), 369–383. https://doi.org/10.7150/thno.21397

Li, J., Peng, C., Guo, Z., Shi, C., Zhuang, R., Hong, X., Wang, X., Xu, D., Zhang, P., Zhang, D., Liu, T., Su, X., & Zhang, X. (2018). Radioiodinated Pentixather for SPECT Imaging of Expression of the Chemokine Receptor CXCR4 in Rat Myocardial-Infarction-Reperfusion Models. Analytical Chemistry, 90(15), 9614–9620. https://doi.org/10.1021/acs.analchem.8b02553

Schottelius, M., Osl, T., Poschenrieder, A., Hoffmann, F., Beykan, S., Hänscheid, H., Schirbel, A., Buck, A. K., Kropf, S., Schwaiger, M., Keller, U., Lassmann, M., & Wester, H.-J. (2017). [177Lu]pentixather: Comprehensive Preclinical Characterization of a First CXCR4-directed Endoradiotherapeutic Agent. Theranostics, 7(9), 2350–2362. https://doi.org/10.7150/thno.19119

Oncology

Demirkol, M. O., Özkan, A., Uçar, B., Wester, H.-J., & Ferhanoglu, B. (2021). Extramedullary Relapsed Multiple Myeloma Treatment With 177Lu-Labeled CXCR4 Endoradiotherapy and Dosimetric Results. Clinical Nuclear Medicine, Publish Ahead of Print. https://doi.org/10.1097/RLU.0000000000003705

Habringer, S., Lapa, C., Herhaus, P., Schottelius, M., Istvanffy, R., Steiger, K., Slotta-Huspenina, J., Schirbel, A., Hänscheid, H., Kircher, S., Buck, A. K., Götze, K., Vick, B., Jeremias, I., Schwaiger, M., Peschel, C., Oostendorp, R., Wester, H.-J., Grigoleit, G.-U., & Keller, U. (2018). Dual Targeting of Acute Leukemia and Supporting Niche by CXCR4-Directed Theranostics. Theranostics, 8(2), 369–383. https://doi.org/10.7150/thno.21397

Herrmann, K., Schottelius, M., Lapa, C., Osl, T., Poschenrieder, A., Hänscheid, H., Lückerath, K., Schreder, M., Bluemel, C., Knott, M., Keller, U., Schirbel, A., Samnick, S., Lassmann, M., Kropf, S., Buck, A. K., Einsele, H., Wester, H.-J., & Knop, S. (2016). First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 57(2), 248–251. https://doi.org/10.2967/jnumed.115.167361

Lapa, C., Hänscheid, H., Kircher, M., Schirbel, A., Wunderlich, G., Werner, R. A., Samnick, S., Kotzerke, J., Einsele, H., Buck, A. K., Wester, H.-J., & Grigoleit, G. U. (2019). Feasibility of CXCR4-Directed Radioligand Therapy in Advanced Diffuse Large B-Cell Lymphoma. Journal of Nuclear Medicine, 60(1), 60–64. https://doi.org/10.2967/jnumed.118.210997

Lapa, C., Herrmann, K., Schirbel, A., Hänscheid, H., Lückerath, K., Schottelius, M., Kircher, M., Werner, R. A., Schreder, M., Samnick, S., Kropf, S., Knop, S., Buck, A. K., Einsele, H., Wester, H.-J., & Kortüm, K. M. (2017). CXCR4-directed endoradiotherapy induces high response rates in extramedullary relapsed Multiple Myeloma. Theranostics, 7(6), 1589–1597. https://doi.org/10.7150/thno.19050

Lapa, C., Lückerath, K., Kircher, S., Hänscheid, H., Grigoleit, G. U., Rosenwald, A., Stolzenburg, A., Kropf, S., Einsele, H., Wester, H.-J., Buck, A. K., Kortüm, K. M., & Schirbel, A. (2019). Potential influence of concomitant chemotherapy on CXCR4 expression in receptor directed endoradiotherapy. British Journal of Haematology, 184(3), 440–443. https://doi.org/10.1111/bjh.15096

Maurer, S., Herhaus, P., Lippenmeyer, R., Hänscheid, H., Kircher, M., Schirbel, A., Maurer, H. C., Buck, A. K., Wester, H.-J., Einsele, H., Grigoleit, G.-U., Keller, U., & Lapa, C. (2019). Side Effects of CXC-Chemokine Receptor 4-Directed Endoradiotherapy with Pentixather Before Hematopoietic Stem Cell Transplantation. Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine, 60(10), 1399–1405. https://doi.org/10.2967/jnumed.118.223420

Inflammatory

Li, X., Kemmer, L., Zhang, X., Kircher, M., Buck, A. K., Wester, H.-J., Hacker, M., & Lapa, C. (2018). Anti-Inflammatory Effects on Atherosclerotic Lesions Induced by CXCR4-Directed Endoradiotherapy. Journal of the American College of Cardiology, 72(1), 122–123. https://doi.org/10.1016/j.jacc.2018.04.035

ABOUT RADIOPHARMACEUTICALS / NUCLEAR MEDICINE

Radiopharmaceuticals are drugs which are a combination of a vector, linker and radionuclide, each having a different function. The vector, e.g. a small molecule, peptide or antibody, is intended to specifically bind to a target tissue (target), e.g. a tumor. The more precisely the vector binds to the target and not to non-targeted tissues, organs or cells, the higher the medical benefit reducing side effects. The linker connects the vector to the radioactive payload to be delivered to the disease burden.

Depending on the type of radiation and the energy, radiopharmaceuticals can be used as a diagnostic agent (DX) or as a therapeutic agent (TX). When used as a diagnostic tool, PET (positron emission tomopraphy) or SPECT (single photon emission computed tomography) detect the radioactivity bound to the target tissue and provide visual information about the disease burden. When used as a therapeutic agent, the radiation and energy of the radionuclide (alpha or beta emitters) is used to incude DNA double strand breaks followed by cell death. Whereas the vector is often the same for the diagnostic and therapeutic agent the radionuclide differs in type of radiation and energy. This combination of diagnostic and therapeutic enables the THERANOSTIC approach of FIND, FIGHT and FOLLOW for a specific disease which offers effective personalised patient treatment.

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