*3.2. 11C-Acetate*

11C-acetate is rapidly picked-up by cells and metabolized into acetyl-CoA by the key enzyme acetyl-CoA synthase, which is overexpressed in certain cancer cells [39]. The use of 11C-acetate in MM can be justified by the elevated lipid synthesis in proliferating abnormal plasma cells as reported by studies with myeloma cell lines [40].

Similarly to radiolabeled choline, the first report of 11C-acetate uptake in myeloma lesions was an incidental finding [41]. In total, two comparative studies of 11C-acetate with 18F-FDG have been published thus far. Ho et al. evaluated a heterogeneous group of 35 untreated patients (26 with symptomatic MM, 5 with SMM, and 4 with MGUS), 9 of which undergoing also dual tracer follow-up PET/CT. The authors reported a significantly higher overall sensitivity for symptomatic MM with 11C-acetate than with 18F-FDG (84.6% vs. 57.7%), while the specificity for 11C-acetate and 18F-FDG PET/CT was 100% and, 93.1% respectively. Furthermore, all indolent plasma cell neoplasms (SMM and MUGS) were negative by 11C-acetate PET, whereas 2 cases of MGUS were false-positive by 18F-FDG [42]. A similar study was published a few months later by Lin et al. in 15 untreated MM patients examined with both tracers at diagnosis, 13 of which being evaluated with a repeated dual-tracer examination after completion of induction treatment. They found a higher detection rate for both diffuse and focal myeloma lesions at initial staging using 11C-acetate than 18F-FDG. Moreover, after treatment the diffuse bone marrow 11C-acetate uptake showed a statistically significant difference in SUVmax reductions between patients with at least a very good partial response and those with at most a partial response. Such a difference between patients in these two response groups was not observed with 18F-FDG PET/CT [43].

In summary, these preliminary findings imply a potential role for 11C-acetate PET/CT for the evaluation of patients with MM. Nevertheless, practical and logistical considerations are raised due to the fact that the synthesis of the tracer requires technical expertise and an on-site cyclotron.
