CXCR4 PET/CT Scan Is Superior to FDG PET/CT Scan in Accurately Defining Marginal Zone Lymphoma Nodal and Extranodal Involvement
Authors: Duell Johannes , Rosenwald Andreas , Krummenast Franziska , Buck Andreas , Einsele Hermann , Topp Max S. , Lapa Constantin 
Published: October 2019

Abstract
Introduction:
Imaging by PET/CT scan with FDG is the gold standard for initial staging for malignant lymphoma. This sequence is very robust for Hodgkin lymphoma, aggressive lymphomas and follicular lymphoma but lacks sensitivity for marginal zone lymphoma (MZL), irrespectively of the different MZL subsets e.g. mucosa-associated lymphoid tissue (MALT), and nodal marginal lymphoma (NMZL ), splenic marginal zone lymphoma (sMZL) and extranodal marginal zone lymphoma (eNMZL). Limited disease of MZL (Stage I/II) are commonly treated by irradiation. Extensive disease (Stage III/IV) is either followed by watch and wait if clinically asymptomatic and or treated with anti-CD20 directed immune chemotherapy if clinically prudent.
Hence, better diagnostic procedure are highly warranted to improve the accuracy of the Ann Arbor staging in MZL for Stage adapted treatment of MZL patients.
Method:
Nineteen patients with newly diagnosed MZL (13 MALT, 5 NMZL, 1 sMZL) received a PET/CT scan with FDG as tracer and bone biopsy as standard staging procedures. All patients with MALT MZL were further subject to gastric endoscopy and coloscopy with tissue biopsy. All patients received in addition a CXCR4-directed radiotracer [68Ga] Pentixafor PET/CT scan, which has shown to be of diagnostic value in multiple myeloma patients. If a lesion was negative by FDG PET scan but positive by CXCR4 PET, additional tissue was acquired to confirm MZL infiltration by immunohistochemistry in selected patients.
Results:
From 05/2017 to 05/2018 nineteen newly diagnosed MZL were staged by conventional PET/CT scan resulting in 2 patients with limited disease status and 12 in extensive disease status. 5 patients had no lesions with FDG PET confirmed as a false negative readout. Utilizing CXCR4 PET/CT SCAN 4 had limited disease and 15 had extensive disease. Only 1 patient with a minimal gastral infiltration and low proliferation frequency was not detected. All bone marrow infiltrations could be detected by CXCR4 (3 out of 3) but none with FDG PET scan. For intestinal involvement of the lymphoma 2 out of 3 patients were true positive (confirmed by biopsy) with CXCR4 PET scan but 0 out of 3 patients with FDG PET scan. 12 out of 13 patients with MALT Lymphoma were PET CXCR4 positive in all leasions. In contrast, only 6 out 13 patients with MALT could be detected with FDG PET scan. In the group of NMZL 5/5 patients demonstrated CXCR4 PET positivity. In contrast only 5 out 5 had a FDG uptake. For the single case of sMZL, the CXCR4 PET was positive but on FDG PET negative.
Taken together, 94.7% of the MZL patients were positive by CXCR4 PET/CT scan but only 42.1% with FDG PET CT scans. In addition, CXCR4 PET showed also uptake in the bone marrow and GI tract in most cases with corresponding involvement whereas FDG/PET missed this involvement all patients.
Conclusion:
CXCR4 PET adapted staging of newly diagnosed marginal zone lymphoma has the potential of becoming the new standard for MZL staging and allocating MZL to the respective front line therapy algorithms. Larger studies are highly warranted to confirm these findings in the future.
Figure. Figure.

Disclosures
Topp: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding; F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer Ingelheim: Research Funding; Regeneron Pharmaceuticals, Inc.: Honoraria, Research Funding.