Theranostic applications of CXCR4-targeted imaging ligands in lymphoma: integrating diagnosis and precision therapy

C-X-C chemokine receptor 4 (CXCR4) is a G protein-coupled receptor implicated in immune regulation, tumor progression, and therapy resistance.In lymphoma, CXCR4 overexpression promotes malignant cell survival via microenvironmental retention and activation of pro-survival pathways, correlating with poor prognosis.Its extracellular localization makes it a strong candidate for selective molecular imaging and targeted therapy.This review summarizes recent advances in CXCR4-targeted agents for lymphoma.Peptidebased radiotracers ( 68 Ga-Pentixafor, [ 18 F]AlF-NOTA-QHY-04, [ 68 Ga]Ga-BL02) and small molecules ([ 64 Cu]AMD3100, [ 18 F]MCFB) offer high specificity and favorable pharmacokinetics for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging.Therapeutic strategies include peptide antagonists (BL-8040, Balixafortide), radioligand therapies ([ 177 Lu]Pentixather, [ 177 Lu]Lu-BL02), small-molecule inhibitors (Plerixafor, WK1), and monoclonal antibodies (PF-06747143, Ulocuplomab, LY2624587).These approaches have demonstrated efficacy in reducing tumor burden and enhancing chemosensitivity.Key challenges include offtarget uptake due to physiological CXCR4 expression and compensatory signaling via CXCR7.Future directions involve dual-receptor targeting, nanoparticle-based delivery, and integration into precision oncology for both hematologic and solid tumors.