CXCR4-targeted [68Ga]Ga-PentixaFor PET/CT improves staging and alters management in marginal zone lymphoma: a prospectively recruited head-to-head study with [18F]FDG.

Abstract

Background: Marginal zone lymphoma (MZL) exhibits substantial clinical heterogeneity, necessitating accurate whole-body tumor burden assessment and early risk stratification. However, conventional [¹⁸F]FDG PET/CT is limited in both anatomical staging and in vivo biological characterization. This prospectively recruiting study conducted a head-to-head comparison of the CXCR4-targeted tracer [⁶⁸Ga]Ga-PentixaFor and [¹⁸F]FDG in treatment-naïve patients to evaluate their complementary value in improving staging accuracy and their association with early treatment response.

Methods: Forty-one treatment-naïve MZL patients prospectively underwent dual-tracer PET/CT prior to therapy. Lesion detection rates, stage migration, and management modifications were systematically assessed. The prognostic value of baseline imaging parameters for interim treatment response was also analyzed.

Results: [⁶⁸Ga]Ga-PentixaFor demonstrated significantly higher lesion detection rates than [¹⁸F]FDG, particularly for gastric (72.0% vs. 40.0%) and nodal involvement (97.4% vs. 39.7%), with a superior target-to-background ratio (median TBR_liver: 5.55 vs. 2.42, p < 0.01). CXCR4-targeted imaging resulted in disease upstaging in 26.8% of patients (overall stage migration: 29.3%) and led to management modifications in 56.1%. Regarding therapeutic outcomes, higher baseline [⁶⁸Ga]Ga-PentixaFor SUVmax (> 7.96) was associated with lower complete remission (CR) rates. Notably, dual-tracer phenotyping further demonstrated decreasing CR rates across double-negative, single-positive, and double-positive groups (100%, 61.5%, and 36.4%, respectively).

Conclusion: [⁶⁸Ga]Ga-PentixaFor PET/CT significantly outperforms [¹⁸F]FDG in initial staging of MZL and has a substantial impact on clinical management. Importantly, dual-tracer imaging shows potential as a novel, non-invasive biomarker for in vivo phenotypic characterization, which is associated with early therapeutic outcomes and the identification of high-risk patients.