CXCR4 PET imaging of mantle cell lymphoma using [⁶⁸Ga]Pentixafor: comparison with [¹⁸F]FDG-PET

For PET imaging of mantle cell lymphoma (MCL), [¹⁸F]FDG (2-deoxy-2-[¹⁸F]fluoro-D-glucose) is the currently recommended radiotracer, although uptake is variable and bone marrow evaluation is limited. In this prospective study, we evaluated the novel CXCR4 (G-protein-coupled C-X-C chemokine receptor type 4) tracer [⁶⁸Ga]Pentixafor in MCL patients, and compared it to [¹⁸F]FDG. Methods: MCL patients underwent [⁶⁸Ga]Pentixafor-PET/MRI, and, if required for routine purposes, also [¹⁸F]FDG-PET/MRI, before treatment. PET was evaluated separately for 23 anatomic regions (12 lymph node stations and 11 organs/tissues), using MRI as the main reference standard. Standardized uptake values (SUV_max and SUV_mean) and tumor-to-background ratios (TBR_blood and TBR_liver) were calculated. General Estimation Equations (GEE) were used to compare [⁶⁸Ga]Pentixafor-PET and [¹⁸F]FDG-PET sensitivities and positive predictive values (PPV). For bone marrow involvement, where biopsy served as the main reference standard, and splenic involvement, receiver operating characteristic curves were used to determine the optimal SUV and TBR cut-off values, and areas under the curve (AUC) were calculated. Results: Twenty-two MCL patients were included. [⁶⁸Ga]Pentixafor-PET sensitivity (100%) was significantly higher than for [¹⁸F]FDG-PET (75.2%) (P<0.001), and PPV was slightly, but not significantly lower (94.0%.vs. 96.5%; P=0.21). SUVs and TBRs were significantly higher for [⁶⁸Ga]Pentixafor-PET than for [¹⁸F]FDG-PET (P<0.001 in all cases); the greatest difference was observed for mean TBR_blood, with 4.9 for [⁶⁸Ga]Pentixafor-PET and 2.0 for [¹⁸F]FDG-PET. For bone marrow involvement, [⁶⁸Ga]Pentixafor-PET SUV_mean showed an AUC of 0.92; and for splenic involvement, TBR_blood showed an AUC of 0.81. Conclusion: [⁶⁸Ga]Pentixafor-PET may become an alternative to [¹⁸F]FDG-PET in MCL patients, showing clearly higher detection rates and better tumor-to-background contrast.