Nuclear Medicine Application of Pentixafor/Pentixather Targeting CXCR4 for Imaging and Therapy in Related Disease

C-X-C-motif chemokine receptor 4 (CXCR4) is a novel predictive biomarker for metastasis and poor prognosis in individuals with malignancies. CXCL12 is the only cognate ligand of CXCR4. CXCL12/CXCR4 signaling pathways are involved in the cross-talk among cancer cells, T cells, stromal cells, and their microenvironments, including the regulation and direction of T cell migration (chemotaxis), proliferation, and differentiation of immature progenitor stem cells. As CXCR4 overexpression is related to tumor prognosis, it is essential to quantitatively evaluate CXCR4 expression levels in vivo. ⁶⁸Ga-Pentixafor, as a radiolabeled tracer, shows high specificity and affinity for CXCR4 in tumors. Thus, CXCR4-directed imaging with ⁶⁸Ga-Pentixafor has been investigated to evaluate CXCR4 expression in patients non-invasively. In recent years, many small cohorts, including those of individuals with hematologic malignancies, solid tumors, and cardiovascular and infectious diseases, have been reported. So far, ⁶⁸Ga-Pentixafor has been used successfully in individuals with hematologic malignancies. In addition, Lutetium-177 (¹⁷⁷Lu) or Yttrium-90 (⁹⁰Y)-labeled Pentixather (an analog of Pentixafor) suggested high potential applicability in tumor endoradiotherapy (ERT) with CXCR4 overexpression. Patients with advanced-stage multiple myeloma, refractory acute leukemia, and diffuse large B-cell lymphoma received a certain amount of ¹⁷⁷Lu-Pentixather or ⁹⁰Y-Pentixather. This review aimed to overview the current CXCR4-directed positron emission computed tomography (PET) molecular imaging based on Pentixafor in several diseases and ERT.