Peter Herhaus1, Jana Lipkova2, Felicitas Lammer3, Igor Yakushev4, Tibor Vag4, Julia Slotta-Huspenina5, Stefan Habringer3,6, Constantin Lapa7,8, Tobias Pukrop9, Dirk Hellwig10, Benedikt Wiestler2, Andreas K Buck7, Martina Deckert11, Hans-Jürgen Wester12, Florian Bassermann1, Markus Schwaiger4, Wolfgang Weber2, Björn Menze13, Ulrich Keller14,3,15,16. 1. Internal Medicine III, School of Medicine, Technische Universität München, Munich, Germany. 2. Department of Neuroradiology, School of Medicine, Technische Universität München, Munich, Germany. 3. Department of Hematology, Oncology, and Tumor Immunology (Campus Benjamin Franklin), Charité-Universitätsmedizin Berlin, Berlin, Germany. 4. Department of Nuclear Medicine, School of Medicine, Technische Universität München, Munich, Germany. 5. Institute of Pathology, Technische Universität München, Munich, Germany. 6. Berlin Institute of Health (BIH), Berlin, Germany. 7. Department of Nuclear Medicine, Universitätsklinikum Würzburg, Würzburg, Germany. 8. Department of Nuclear Medicine, University Hospital Augsburg, Augsburg, Germany. 9. Internal Medicine III, Universitätsklinikum Regensburg, Regensburg, Germany. 10. Department of Nuclear Medicine, Universitätsklinikum Regensburg, Regensburg, Germany. 11. Insitute of Neuropathology, Faculty of Medicine, University of Cologne, and University Hospital Cologne, Cologne, Germany. 12. Institute of Pharmaceutical Radiochemistry, Technische Universität München, Munich, Germany. 13. Informatics Department, Technische Universität München, Munich, Germany. 14. Internal Medicine III, School of Medicine, Technische Universität München, Munich, Germany ulrich.keller@charite.de. 15. Max Delbrück Center for Molecular Medicine, Berlin, Germany; and. 16. German Cancer Research Center and German Cancer Consortium, Heidelberg, Germany.
Abstract
C-X-C chemokine receptor 4 (CXCR4) is a transmembrane chemokine receptor involved in growth, survival, and dissemination of cancer, including aggressive B-cell lymphoma. MRI is the standard imaging technology for central nervous system (CNS) involvement of B-cell lymphoma and provides high sensitivity but moderate specificity. Therefore, novel molecular and functional imaging strategies are urgently required. Methods: In this proof-of-concept study, 11 patients with lymphoma of the CNS (8 primary and 3 secondary involvement) were imaged with the CXCR4-directed PET tracer 68Ga-pentixafor. To evaluate the predictive value of this imaging modality, treatment response, as determined by MRI, was correlated with quantification of CXCR4 expression by 68Ga-pentixafor PET in vivo before initiation of treatment in 7 of 11 patients. Results: 68Ga-pentixafor PET showed excellent contrast with the surrounding brain parenchyma in all patients with active disease. Furthermore, initial CXCR4 uptake determined by PET correlated with subsequent treatment response as assessed by MRI. Conclusion: 68Ga-pentixafor PET represents a novel diagnostic tool for CNS lymphoma with potential implications for theranostic approaches as well as response and risk assessment.
C-X-C chemokine receptor 4 (CXCR4) is a transmembrane chemokine receptor involved in growth, survival, and dissemination of cancer, including aggressive B-cell lymphoma. MRI is the standard imaging technology for central nervous system (CNS) involvement of B-cell lymphoma and provides high sensitivity but moderate specificity. Therefore, novel molecular and functional imaging strategies are urgently required. Methods: In this proof-of-concept study, 11 patients with lymphoma of the CNS (8 primary and 3 secondary involvement) were imaged with the CXCR4-directed PET tracer 68Ga-pentixafor. To evaluate the predictive value of this imaging modality, treatment response, as determined by MRI, was correlated with quantification of CXCR4 expression by 68Ga-pentixafor PET in vivo before initiation of treatment in 7 of 11 patients. Results:68Ga-pentixafor PET showed excellent contrast with the surrounding brain parenchyma in all patients with active disease. Furthermore, initial CXCR4 uptake determined by PET correlated with subsequent treatment response as assessed by MRI. Conclusion:68Ga-pentixafor PET represents a novel diagnostic tool for CNS lymphoma with potential implications for theranostic approaches as well as response and risk assessment.
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