11C-Methionine-PET in Multiple Myeloma: A Combined Study from Two Different Institutions

Abstract

¹¹C-methionine (MET) has recently emerged as an accurate marker of tumor burden and disease activity in patients with multiple myeloma (MM). This dual-center study aimed at further corroboration of the superiority of MET as positron emission tomography (PET) tracer for staging and re-staging MM, as compared to ¹⁸F-2`-deoxy-2`-fluoro-D-glucose (FDG). 78 patients with a history of solitary plasmacytoma (n=4), smoldering MM (SMM, n=5), and symptomatic MM (n=69) underwent both MET- and FDG-PET/computed tomography (CT) at the University Centers of Würzburg, Germany and Navarra, Spain. Scans were compared on a patient and on a lesion basis. Inter-reader agreement was also evaluated. In 2 patients, tumor biopsies for verification of discordant imaging results were available. MET-PET detected focal lesions (FL) in 59/78 subjects (75.6%), whereas FDG-PET/CT showed lesions in only 47 patients (60.3%; p<0.01), accordingly disease activity would have been missed in 12 patients. Directed biopsies of discordant results confirmed MET-PET/CT results in both cases. MET depicted more FL in 44 patients (56.4%; p<0.01), whereas in two patients (2/78), FDG proved superior. In the remainder (41.0%, 32/78), both tracers yielded comparable results. Inter-reader agreement for MET was higher than for FDG (κ = 0.82 vs κ = 0.72). This study demonstrates higher sensitivity of MET in comparison to standard FDG to detect intra- and extramedullary MM including histologic evidence of FDG-negative, viable disease exclusively detectable by MET-PET/CT. MET holds the potential to replace FDG as functional imaging standard for staging and re-staging of MM.

Keywords: 11C-methionine; FDG.; PET/CT; multiple myeloma.

Figure 1

Display of a patient (patient #8) with Ig G κ SMM. Imaging with both tracers was performed on the same day. Whereas PET/CT with FDG did not depict hypermetabolic foci suspicious for active MM, MET demonstrated increased tracer uptake throughout the skeleton. Bone marrow biopsy revealed 45% clonal plasma cells. Blood tests showed an IgG κ M-spike of 8.6 g/dl, free light chain (FLC) κ levels of 1.22 mg/dl, and FLC λ levels of 0.13 mg/dl (ratio κ/λ= 9.38). Bence-Jones proteinuria was 191 mg/24 h-collected urine. The patient was diagnosed of high-risk smoldering MM and started treatment in a Spanish myeloma group clinical trial. After induction and consolidation treatment, she is in stringent complete response with MRD negativity as assessed by flow cytometry.

Figure 2

Display of a patient (patient #57) with a history of Ig G λ MM. Imaging with both tracers was performed within 6 days. PET/CT with FDG depicted multiple hypermetabolic foci consistent with active MM which were partly missed by MET (transaxial slice of thoracic vertebra Th 7, arrows).

Figure 3

Display of a patient (patient #60) with a history of Ig A λ MM. Imaging with both tracers depicted multiple hypermetabolic foci consistent with active MM. However, due to high physiologic uptake, extramedullary liver lesions were missed by MET-PET (arrows).

Figure 4

Display of a patient (patient #71) with a history of Ig G κ MM after treatment initiation with lenalidomide and dexamethasone. The patient was referred for further evaluation of a painful, growing lesion in the proximal third of the right clavicle. The lesion demonstrated focal FDG uptake. In contrast, MET-PET was negative (arrows). Biopsy was performed and no tumor infiltration was demonstrated, consistent with a benign fracture. MET-PET additionally revealed partial response with inhomogeneous, focally increased tracer uptake of the axial as well as appendicular skeleton, whereas FDG-PET did not depict hypermetabolic foci suspicious for active MM in these locations.

Figure 5

Display of a patient (patient #3) with a history of solitary plasmacytoma treated with radiotherapy. Imaging with both tracers was performed on the same day. Whereas PET/CT with FDG did not depict hypermetabolic foci suspicious for active MM, MET demonstrated focally increased tracer uptake in the left zygomatic bone (arrows). Biopsy confirmed monoclonal plasma cell infiltration.