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

For PET imaging of mantle cell lymphoma (MCL), [(18)F]FDG (2-deoxy-2-[(18)F]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 [(68)Ga]Pentixafor in MCL patients, and compared it to [(18)F]FDG. Methods: MCL patients underwent [(68)Ga]Pentixafor-PET/MRI, and, if required for routine purposes, also [(18)F]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 [(68)Ga]Pentixafor-PET and [(18)F]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. [(68)Ga]Pentixafor-PET sensitivity (100%) was significantly higher than for [(18)F]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 [(68)Ga]Pentixafor-PET than for [(18)F]FDG-PET (P<0.001 in all cases); the greatest difference was observed for mean TBR(blood), with 4.9 for [(68)Ga]Pentixafor-PET and 2.0 for [(18)F]FDG-PET. For bone marrow involvement, [(68)Ga]Pentixafor-PET SUV(mean) showed an AUC of 0.92; and for splenic involvement, TBR(blood) showed an AUC of 0.81. Conclusion: [(68)Ga]Pentixafor-PET may become an alternative to [(18)F]FDG-PET in MCL patients, showing clearly higher detection rates and better tumor-to-background contrast.