: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.