Improved Primary Staging of Marginal-Zone Lymphoma by Addition of CXCR4-Directed PET/CT

Abstract

Positron emission tomography/computed tomography (PET/CT) with 18 Ffluorodesoxyglucose (FDG) is an integral component in the primary staging of most lymphomas. However, its utility is limited in marginal zone lymphoma (MZL) due to inconsistent FDG avidity. One diagnostic alternative could be the targeting of CXC-motif chemokine receptor 4 (CXCR4), shown to be expressed by MZL cells. This study investigated the value of adding CXCR4-directed 68 Ga-Pentixafor PET/CT (CXCR4 PET/CT) to conventional staging. Methods22 newly diagnosed MZL patients were staged conventionally and with CXCR4 PET/CT.Lesions exclusively identified by CXCR4 PET/CT were biopsied as standard of reference and compared to imaging results. The impact of CXCR4-directed imaging on staging results and treatment protocol was assessed. ResultsCXCR4 PET/CT correctly identified all patients with viable MZL and was superior to conventional staging (P < 0.001). CXCR4-directed imaging results were validated by confirmation of MZL in 16/18 PET-guided biopsy samples. Inclusion of CXCR4 PET/CT in primary staging significantly impacted staging results in almost half, and treatment protocols in one third of patients (upstaging, n = 7; downstaging, n = 3; treatment change, n = 8; P < 0.03). ConclusionsCXCR4 PET/CT is a suitable tool in primary staging of MZL and holds the potential to improve existing diagnostic algorithms.

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].…”

Whole-Body [18F]FDG PET/CT Can Alter Diagnosis in Patients with Suspected Rheumatic Disease

“…Patients fasted at least 6 h prior to injection of 289.1 ± 38.5 MBq [ 18 F]FDG. PET/CT scans were acquired after 60 min post-injection, using non-contrast-enhanced CT with CARE Dose 4D with the following parameters: 160 mAs, 120 kV, 512 × 512 matrix, 5 mm slice thickness, slice collimation 64 × 0.6 mm [13]. PET data were reconstructed according to standard protocols as described in [13].…”