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

Figures

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  Figure 1. Pre-therapeutic [68Ga]Pentixafor-PET/MRI and [18F]FDG-PET/MRI of an 82-year-old female MCL patient. [68Ga]Pentixafor-PET detects considerably more nodal lymphoma manifestations than [18F]FDG-PET, and stronger tracer uptake in several lesions/regions. All lymph nodes with focal increased [68Ga]Pentixafor uptake corresponded to clearly enlarged lymph nodes on diffusion-weighted MRI (DWI). Representative examples of such [68Ga]Pentixafor-PET-positive lesions with no or low [18F]FDG uptake, but obvious lymphadenopathy on DWI, are marked by blue arrowheads (left axially, retroperitoneal/periaortic, and right pelvic regions).

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  Figure 2. Pre-therapeutic [68Ga]Pentixafor-PET/MRI and [18F]FDG-PET/MRI of a 61-year-old male MCL patient. While the majority of supra- and infradiaphragmatic nodal lymphoma manifestations show both an increased [68Ga]Pentixafor and [18F]FDG uptake, the extranodal gastric lymphoma manifestation and an adjacent enlarged lymph node (blue arrowheads) are only positive on [68Ga]Pentixafor-PET, but not on [18F]FDG-PET. Diffusion-weighted MRI (DWI) confirmed the presence of both lesions, which show a low signal on the apparent diffusion coefficient (ADC) map, reflecting the high cell density typically observed in lymphomas.

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  Figure 3. Pre-therapeutic [68Ga]Pentixafor-PET/MRI and [18F]FDG-PET/MRI of a 52-year-old male MCL patient. Several infradiaphragmatic nodal lymphoma manifestations (blue arrowheads) that show strong [68Ga]Pentixafor uptake on PET (top) and fused color-coded PET/MRI (bottom) show only moderate-to-low [18F]FDG uptake that does not, or only slightly, exceed the [18F]FDG uptake of the liver. Consequently, measured tumor-to-background ratios (TBRblood, TBRliver) are higher for [68Ga]Pentixafor-PET than for [18F]FDG-PET.

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  Figure 4. Bland-Altman plots illustrate paired differences between [68Ga]Pentixafor-PET and [18F]FDG-PET standardized uptake values (SUV) and tumor-to-background ratios (TBR).

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  Figure 5. Receiver operating characteristic (ROC) curves that illustrate the respective performances of [68Ga]Pentixafor-PET standardized uptake values (SUV) and tumor-to-background ratios (TBR) for detection of bone marrow and splenic involvement.

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  Figure 6. Double staining of CXCR4 (brown) and Cyclin D1 (nuclear, red) showing strong membraneous expression of CXCR4 on MCL cells in the center of neoplastic nodules, whereas in diffuse areas (depicted on the left), mainly dot-like intracellular signals are denoted.