Assessment of glucose metabolism and cellular proliferation in multiple myeloma: a first report on combined 18F-FDG and 18F-FLT PET/CT imaging

Background: Despite the significant upgrading in recent years of the role of F-18-FDG PET/CT in multiple myeloma (MM) diagnostics, there is a still unmet need for myeloma-specific radiotracers. 3'-Deoxy-3'-[F-18]fluorothymidine (F-18-FLT) is the most studied cellular proliferation PET agent, considered a potentially new myeloma functional imaging tracer. The aim of this pilot study was to evaluate F-18-FLT PET/CT in imaging of MM patients, in the context of its combined use with F-18-FDG PET/CT. Results: Eight patients, four suffering from symptomatic MM and four suffering from smoldering MM (SMM), were enrolled in the study. All patients underwent F-18-FDG PET/CT and F-18-FLT PET/CT imaging by means of static (whole body) and dynamic PET/CT of the lower abdomen and pelvis (dPET/CT) in two consecutive days. The evaluation of PET/CT studies was based on qualitative evaluation, semi-quantitative (SUV) calculation, and quantitative analysis based on two-tissue compartment modeling. F-18-FDG PET/CT demonstrated focal, F-18-FDG avid, MM-indicative bone marrow lesions in five patients. In contrary, F-18-FLT PET/CT showed focal, F-18-FLT avid, myeloma-indicative lesions in only two patients. In total, 48 F-18-FDG avid, focal, MM-indicative lesions were detected with F-18-FDG PET/CT, while 17 F-18-FLT avid, focal, MM-indicative lesions were detected with F-18-FLT PET/CT. The number of myeloma-indicative lesions was significantly higher for F-18-FDG PET/CT than for F-18-FLT PET/CT. A common finding was a mismatch of focally increased F-18-FDG uptake and reduced F-18-FLT uptake (lower than the surrounding bone marrow). Moreover, F-18-FLT PET/CT was characterized by high background activity in the bone marrow compartment, further complicating the evaluation of bone marrow lesions. Semi-quantitative evaluation revealed that both SUVmean and SUVmax were significantly higher for F-18-FLT than for F-18-FDG in both MM lesions and reference tissue. SUV values were higher in MM lesions than in reference bone marrow for both tracers. Conclusion: Despite the limited number of patients analyzed in this pilot study, the first results of the trial indicate that F-18-FLT does not seem suitable as a single tracer in MM diagnostics. Further studies with a larger patient population are warranted to generalize the herein presented results.