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.

Fully-automated production of [68Ga]Ga-PentixaFor on the module Modular Lab-PharmTracer

“…inflammatory conditions (Bouter et al, 2018). Examples of clinical applications in oncology are the detection of neuroendocrine tumors, multiple myeloma (Pan et al, 2018), glioma, leukemia (Mayerhoefer et al, 2018) or lymphoma (Luo et al, 2019;Haug et al, 2019). Since the precursor PentixaFor was made available until summer 2018 only for use by the synthesis module from Scintomics®, only hospitals that operated a Scintomics® module were able to prepare [ 68 Ga]Ga-PentixaFor.…”

Preliminary evidence of imaging of chemokine receptor-4-targeted PET/CT with [68Ga]pentixafor in non-Hodgkin lymphoma: comparison to [18F]FDG

“…Stollberg S. and the colleagues found that CXCR4 expression was present at a high intensity in 92% of the cases [ 22 ]. In a recent study of MALT lymphoma, 33/36 patients were positive on [ 68 Ga]pentixafor PET/MRI showing a high uptake of [ 68 Ga]pentixafor [ 10 ]. Another head-to-head comparison study of [ 68 Ga]pentixafor and [ 18 F]FDG revealed that 95.2% of marginal zone lymphoma patients had positive lesions on [ 68 Ga]pentixafor PET/CT, as compared to only 42.9% of the patients who were positive on [ 18 F]FDG PET/CT [ 23 ].…”

“…The first clinical application of [ 68 Ga]pentixafor PET has been carried out in patients with non-Hodgkin lymphoma and multiple myeloma, which confirmed the CXCR4 expression in these lymphoproliferative diseases as a proof-of-concept [ 4 ]. Since then, most studies of [ 68 Ga]pentixafor were focused on evaluation of hematologic malignancies, for example, multiple myeloma [ 1 , 5 – 7 ], Waldenström macroglobulinemia/lymphoplasmacytic lymphoma [ 8 , 9 ], mucosa associated lymphoid tissue (MALT) lymphoma [ 10 ], chronic lymphocytic leukemia [ 11 ], and acute myeloid leukemia [ 12 , 13 ]. Some studies showed remarkable superiority of [ 68 Ga]pentixafor PET in detecting tumors and staging of the disease when compared with [ 18 F]FDG PET [ 5 , 7 , 8 ].…”

FDG-PET/CT, a Promising Exam for Detecting High-Risk Myeloma Patients?

“…They also demonstrated the potential of CXCR4 as a theranostic target in MM patients in a pilot study confirming the feasibility of CXCR4-directed radionuclide therapy using 177 Lu or 90 Y-CXCR4 ligand (pentixather) as a novel treatment approach for MM [ 39 ]. Interestingly, compared to 18 FDG, 68 Ga-pentixafor also seems to be a promising imaging tool for assessment of other related blood cancers including MALT lymphoma [ 40 ], Waldenström macroglobulinemia, lymphoplasmacytic lymphoma [ 41 ] and primary central nervous system lymphoma [ 42 ]. Furthemore, the use of 11C-methionine (MET) in MM also seems to have a promising future.…”