The CXCR4-targeted theranostics era: a comprehensive review of a decade of progress (2015-2025)

Over the past decade, theranostics targeting the chemokine receptor CXCR4 have evolved from a promising concept into a clinical reality, revolutionizing the management of a diverse spectrum of diseases. This paradigm shift has been fueled by the development of [⁶⁸Ga]Pentixafor, a high-affinity PET radiotracer that enables the precise, non-invasive visualization of CXCR4 expression in vivo. Its diagnostic prowess extends beyond conventional oncology, demonstrating superior performance to [¹⁸F]FDG in hematologic malignancies and offering critical decision-making insights for endocrine disorders and inflammatory conditions. Seamlessly completing the theranostic loop, the therapeutic counterparts [¹⁷⁷Lu]/[⁹⁰Y]Pentixather deliver targeted radiotherapy to CXCR4-expressing tissues, with pioneering applications in advanced multiple myeloma and acute myeloid leukemia establishing a compelling safety and efficacy profile. While challenges in target heterogeneity and toxicity persist, the future of CXCR4-targeted theranostics is bright, poised for advancement through combinatorial immunotherapies, alpha-emitting radionuclides, and artificial intelligence-driven patient stratification. This review comprehensively synthesizes a decade of progress, affirming CXCR4-targeted theranostics as a cornerstone of precision medicine that faithfully adheres to the "see what you treat, treat what you see" philosophy.