The C–X–C chemokine receptor 4 (CXCR4) and its natural ligand CXCL12 are key factors in the process of cell migration, homing of hematopoietic stem cells to the bone marrow, and represent important mediators of angiogenesis and cell proliferation. In many pathological conditions, such as multiple myeloma, high CXCR4 expression is frequently observed and associated with tumor dissemination as well as prognosis. This makes CXCR4 an attractive target for imaging and treatment of malignant diseases.
Recently, radiolabeled analogs of CXCR4 antagonists (e.g., [68Ga]Pentixafor) have been introduced for non-invasive imaging of CXCR4 expression in preclinical and humans models using positron emission tomography techniques. Furthermore, a therapeutic strategy is also possible with the addition of beta emitter-labeled antagonists (i.e., [177Lu]/[90Y]Pentixather), already used in small cohorts of multiple myeloma patients with promising results. This chapter reports on current imaging protocols for CXCR4-directed positron emission tomography in multiple myeloma patients. The theranostic approach will not be the subject of extensive revision in this chapter, devoted, almost entirely, to the evaluation of multiple myeloma by CXCR4-PET/CT.
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