Abstract
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Background: Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) is an indolent Non-Hodgkin B lymphoma characterized by accumulation of malignant lymphoplasmacytic cells in bone marrow with excess production of monoclonal immunoglobulin. The role of 18F-FDG might be limited in WM/LPL. 68Ga-Pentixafor, a novel PET tracer with high affinity for chemokine receptor-4 (CXCR4), was recently reported in assessment of several lymphoproliferative diseases. According previous research, there is a high level of CXCR4 expression in B cells of WM/LPL compared to B cells from healthy donors, which makes it possible to be imaged with 68Ga-pentixafor. In this study, we aimed to evaluate the performance of 68Ga-pentixafor PET/CT in WM/LPL, in comparison with 18F-FDG.
Methods: A total of 16 patients diagnosed with WM/LPL in department of hematology of PUMCH were prospectively recruited. 18F-FDG and 68Ga-Pentixafor PET/CT were carried out within 1 week after enrollment. Two experienced nuclear medicine physicians visually assessed PET/CT images with consensus on image interpretation. For 18F-FDG, the intensity of disease was based on 5-point scale of Deauville score, and score 4 was set a positivity cutoff. For 68Ga-Pentixafor, the intensity of involvement was classified as mild, moderate and intense with liver and spleen taken as the reference, and uptake > liver was defined as being positive.
Results: Sixteen patients with WM/LPL (10 male, 6 female; age, 63.5±10.2 yr) were enrolled. Fourteen patients had newly diagnosed WM/LPL, and 2 patients had relapsed disease. 68Ga-Pentixafor PET/CT was visually positive in 16/16 (100%) patients, while 18F-FDG PET/CT was positive in 9/16 (56.3%) patients (Table 1). Bone marrow involvement In 68Ga-Pentixafor PET/CT, 9 patients had intense radioactivity in bone marrow, and 6 patients showed moderate uptake. In 18F-FDG PET/CT, 9 patients had score 4 bone marrow uptake; the remaining 7 patients had score 2-3 bone marrow intensity. Compared with 68Ga-Pentixafor and 18F-FDG, 10 patients had visually higher uptake in bone marrow in 68Ga-Pentixafor PET than in 18F-FDG PET (example in Figure 1A); in 5 patients, the intensity of bone marrow uptake in 68Ga-Pentixafor and 18F-FDG PET was comparable; only 1 patient had higher FDG uptake in bone marrow. Regarding the extent of bone marrow involvement, 68Ga-Pentixafor PET in 7 patients demonstrated more extensive bone marrow disease (example in Figure 1B), specifically involvement in craniofacial bones and distal upper extremity bones. Lymph node involvement In 68Ga-Pentixafor PET/CT, 12/16 (75.0%) patients had positive lymph node involvements (example in Figure 2) affecting the neck, axilla, mediastinum, internal mammary, hepatoduodenal, retroperitoneal, iliac, inguinal, and epitrochlear nodes. However, in 18F-FDG PET/CT, only 2 patients were found with FDG-avid lymph nodes (score 3-4); moreover, 68Ga-Pentixafor PET/CT in these 2 patients detected more lymph nodes with higher radioactivity compared with 18F-FDG. paramedullary and other involvement There was paramedullary disease in 3/16 (18.8%) patients affecting soft tissues around sternum, thoracic vertebrae and presacral space; among them one patient also had involvement of thoracic nerve and sacral nerve root confirmed by electromyography (Figure 2E-2H). 68Ga-Pentixafor PET showed intense radioactivity in the above paramedullary and nerve root involvement; the intensity of FDG uptake was much lower compared with 68Ga-Pentixafor. One patient with central nervous system disease (Bing-Neel syndrome) had markedly increased radioactivity in bilateral choroid plexus in 68Ga-Pentixafor PET/CT that was not FDG-avid, and the abnormal 68Ga-Pentixafor uptake in choroid plexus returned normal after 6 cycles of chemotherapy.
Conclusions: 68Ga-Pentixafor PET/CT showed superiority in evaluation of WM/LPL compared with 18F-FDG.