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Background <p>Marginal zone lymphoma (MZL) exhibits substantial clinical heterogeneity, necessitating accurate whole-body tumor burden assessment and early risk stratification. However, conventional [<sup>18</sup>F]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 [<sup>68</sup>Ga]Ga-PentixaFor and [<sup>18</sup>F]FDG in treatment-naïve patients to evaluate their complementary value in improving staging accuracy and their association with early treatment response.</p> Methods <p>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.</p> Results <p>[<sup>68</sup>Ga]Ga-PentixaFor demonstrated significantly higher lesion detection rates than [<sup>18</sup>F]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<sub>liver</sub>: 5.55 vs. 2.42, <i>p</i> &lt; 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 [<sup>68</sup>Ga]Ga-PentixaFor SUVmax (&gt; 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).</p> Conclusion <p>[<sup>68</sup>Ga]Ga-PentixaFor PET/CT significantly outperforms [<sup>18</sup>F]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.</p> Graphical abstract <p></p>

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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

  • 期刊论文

  • 发表日期：

    2026年6月3日

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  • Zitong Zhang,
  • Haoyuan Hu,
  • Xin Li,
  • Yongzhao Xiang,
  • Limin Gao,
  • Yunyi Liu,
  • Hexiao Huang,
  • Liqun Zou,
  • Ming Jiang,
  • Chong Jiang,
  • Rong Tian

摘要

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 TBRliver: 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.

Graphical abstract