11c-Methionine PET/CT in Assessment of Multiple Myeloma Patients: Comparison to 18f-FDG PET/CT and Prognostic Value Evaluation

Multiple myeloma (MM) is the second most common hematological malignancy and remains incurable despite therapeutic advances. 18F-FDG (FDG) PET/CT is a relevant tool in MM for staging and it is the reference imaging technique for treatment evaluation. However, it has limitations, and investigation of other PET tracers is required. Preliminary results with L-methyl-[11C]- methionine (MET), suggest higher sensitivity than FDG. This study aimed to compare the diagnostic accuracy and prognostic value of FDG and MET in MM patients.

Methods: Fifty-two consecutive patients with MM were prospectively simultaneously evaluated by FDG and MET PET/CT. Bone marrow (BM) uptake patterns and the detection of focal lesions (FL) and extramedullary disease (EMD) were compared. Furthermore, FDG PET parameters with known MM prognostic value were explored for both tracers, as well as total metabolic tumor volume (TMTV), total lesion glycolysis (TLG), and total lesion MET uptake (TLMU).

Results: Median patient age was 61 years (range, 37-83 years), 54% were male, 13% of them were in stage ISS (International Staging System) III, and 31% had high-risk cytogenetics. The population include 8 smoldering MM (SMM), 18 newly diagnosed MM (NDMM) and 26 relapse/refractory patients (RRMM).

In six out the total 52 patients (11%) FDG did not detect active disease while they showed to be positive by MET. It should be noted that 4 out of these 6 patients were SMM. Additionally, MET identified higher number of FL than FDG in more than half of the patients (63%). Moreover, the median values for TMTV and total lesion uptake (TLG/TLMU) were higher upon using MET.

None of the SMM patients has progressed so far. Therefore, the prognostic impact of basal PET cannot be investigated in this cohort. Only 4 out of the 18 NDMM patients have progressed so far. The small number of events in the cohort of NDMM patients precludes a sound prognostic analysis. Nevertheless, progressive patients were associated with a larger number of FL, tumor volume and EMD assessed by both, FDG or MET.

In the RRMM patient cohort, 13 out the total 26 patients analyzed by PET have already progress. Upon using FDG the median number of FL (particularly more than 10), as well as the median values of TLG and TMTV were significantly higher in the group of progressive patients. Almost identical results were observed upon using MET.

Conclusion: This study confirmed the diagnostic and prognostic value of FDG in MM; in addition it highlight that MET although it has higher sensitivity than FDG PET/CT for detection of myeloma lesions, including FL, their optimal cut-off values need to be confirmed in larger series of patients. Finally, we show for the first time, the prognostic value of TMTV and TLMU in the imaging evaluation of MM patients.