Prospective non-invasive evaluation of CXCR4 expression for the diagnosis of MALT lymphoma using [68Ga]Ga-Pentixafor-PET/MRI

Abstract

MALT lymphomas express the chemokine receptor CXCR4 on a regular basis, and [68Ga]Ga-Pentixafor-PET has been shown to quantify CXCR4 expression non-invasively. We, therefore, aimed to evaluate [68Ga]Ga-Pentixafor-PET/MRI for the non-invasive assessment of MALT lymphomas.

Methods: We included 36 MALT lymphoma patients, who had not undergone previous systemic or radiation therapy, in our prospective, IRB-approved, proof-of-concept study. Involved anatomic regions were the orbit (n=14), stomach (n=10), lungs (n=5), and other sites (soft-tissues n=3; adrenal gland, tonsils, parotid gland, and urinary bladder n=1, respectively). MRI sequences included an axial 2-point Dixon T1 VIBE SPAIR 3D sequence for PET attenuation correction; a coronal T2 HASTE sequence; and an axial echo-planar imaging SPAIR-based diffusion-weighted sequence (DWI) obtained during free-breathing (b-values, 50 and 800), with corresponding ADC (apparent diffusion coefficient) maps.

Results: In 33/36 patients, there were MALT lymphomas with an increased uptake of [68Ga]Ga-Pentixafor; all current lymphoma manifestations showed an increased uptake and, accordingly, were positive on the PET/MRI. The remaining three patients had undergone surgery for their orbital MALT lymphomas prior to PET/MRI. Mean SUVmax was 8.6 ± 4.7, mean SUVmean was 4.7 ± 1.8, and mean SUVpeak was 8.0 ± 4.2. The mean SUVmax of the liver was 1.8, and the mean tumor-to-liver ratio was 2.9 ± 2.0. There were no significant differences in SUVmax (P=0.22), SUVmean (P=0.53), SUVpeak (P=0.29), or SUVt/l (P=0.92) between the four anatomic regions (orbit, stomach, lungs, other). The mean tumor volume was 146 ± 499.

Conclusions: Our results thus indicate that [68Ga]Ga-Pentixafor-PET is feasible for the assessment of MALT lymphomas, with a good tumor-to-background ratio in terms of radiotracer uptake.

Keywords: CXCR4; MALT lymphoma; PET; PET/MRI; [68Ga]-Pentixafor.

Figure 1

A patient with biopsy-proven MALT lymphoma of the left adrenal gland. The adrenal MALT lymphoma shows high [⁶⁸Ga]Ga-Pentixafor uptake (A, SUVmax 25.4), and is also well-visualized on the DWI b800 image (B, red arrow, C, fused PET/MRI). In addition, an area of increased uptake on PET is visible in the left orbit (E, yellow arrow), which was initially missed on MRI, but, in retrospect, showed restricted diffusion on the ADC map upon consensus reading (D, yellow arrow); this orbital lesion also proved to be MALT lymphoma at histology.

Figure 2

A patient with biopsy-proven gastric MALT lymphoma. The [⁶⁸Ga]Pentixafor PET shows several areas in the stomach with increased [⁶⁸Ga]Ga-Pentixafor uptake (F, yellow arrow on fused PET/MRI) and restricted diffusion on DWI (E, yellow arrow, D T1 VIBE Dixon), indicating the MALT lymphoma. In addition, there is evidence of an enlarged mesenteric lymph node (A, T1 with restricted diffusion on DWI b_800 (B, red arrow) and markedly increased uptake on PET (C, red arrow on fused PET/MRI), consistent with lymph node involvement.

Figure 3

A 63-year-old patient with MALT lymphoma in the upper lobe / apex of the right lung and adjacent pleura. The lymphoma presents as a large consolidation with strong diffusion restriction (high signal on the DWI image (C) and low signal on the corresponding ADC map (D)). On PET, the lymphoma shows only a moderate uptake of [¹⁸F]FDG (A), indicating moderately increased glucose metabolism, but a strong uptake of [⁶⁸Ga]Ga-Pentixafor, suggesting a high CXCR4 expression (B).