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

Abstract

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.

Pentixafor as a Theranostic Agent in Rectal and Pancreatic Adenocarcinoma: Outcomes From a Pilot Study

“…Although there was no correlation seen in a small subgroup between tumoral IHC expression of CXCR4 and pentixafor avidity via PET, the infiltrating immune cells were the largest contributor of CXCR4 expression in both a mouse EAC model and a larger collection of human retrospective EAC primaries [32,33]. Consistent with this, pentixafor PET scans in the diagnosis of lymphoid malignancies have shown promise, and in some cases have been more diagnostically sensitive than FDG [34,35].…”

In Vivo Targeting of CXCR4—New Horizons

“…Additionally, CXCR4 has recently emerged as an interesting molecular target in marginal zone lymphoma [ 14 , 15 ], gastric mucosa-associated lymphoid tissue (MALT) lymphoma [ 16 ], mantle cell lymphoma [ 17 ], myeloproliferative neoplasms [ 18 ] as well as primary lymphoma of the central nervous system [ 19 ]. In Waldenström macroglobulinemia/lymphoplasmacytic lymphoma, a disease in which about 40% of patients have mutations in the CXCR4 gene, preliminary results with non-invasive PET imaging using [ 68 Ga]Pentixafor have demonstrated promising results in both staging and therapy response assessment.…”

FDG-PET/CT in Lymphoma: Where Do We Go Now?

“…This transmembrane receptor is involved in the cell migration process and in the homing of hematopoietic stem cells to the bone marrow compartment. Several studies reported the use of 68Ga-Pentixafor that showed a high contrast in CXCR4-expressing lymphomas [114][115][116][117]. Furthermore, for a theranostic approach, its therapeutic properties are currently under investigation, radiolabeled with βor α-emitters [118].…”