*2.1. 18F-FDG PET*/*CT in the Diagnosis and Staging of MM*

18F-FDG PET/CT has been proven to be a very useful modality for the whole-body evaluation of the active burden of MM. Its reported sensitivity and specificity for assessment of medullary and extramedullary disease extent ranges from 80–100% [7–12]. The uptake pattern, SUV and different pharmacokinetic parameters of 18F-FDG correlate with the percentage of bone marrow plasma cells [13] (Figure 1).

**Figure 1.** Maximum intensity projection (MIP) PET/CT images of newly diagnosed MM patients before treatment, representing examples of different pathologic patterns of 18F-FDG uptake. (**A**) demonstrates a patient with multiple focal lesions in the skeleton. (**B**) depicts a patient with intense diffuse tracer uptake in the bone marrow of the axial skeleton and the proximal humeri and femora without clearly delineated focal lesions. (**C**) shows a patient with a mixed pattern of 18F-FDG uptake with intense, diffuse uptake in the axial skeleton and multiple, focal bone marrow lesions.

PET/CT has been compared with other imaging modalities and has been shown to be superior to WBXR and comparable to MRI. In particular, a prospective study comparing 18F-FDG PET/CT with WBXR and pelvic-spinal MRI highlighted the superiority of PET/CT to WBXR in 46% of cases (sensitivity 92% vs. 61%). The sensitivity of PET/CT in the spine was inferior to MRI, underestimating the disease in a third of the patients; however, 18F-FDG PET/CT detected sites of active disease in areas outside the field of the MRI view [8]. Similarly, the results of a systematic review of 18 studies comparing the above-mentioned modalities showed a higher sensitivity of MRI at detecting diffuse disease of the spine, while 18F-FDG PET/CT was more sensitive than WBXR with regard to detection of bone lesions [10]. In another systematic review of 17 studies no significant differences were found between 18F-FDG PET/CT (sensitivity 91%, specificity 69%) and MRI (sensitivity 88%, specificity 68%) regarding detection rate of bone disease [11]. Recently, the prospective French IMAJEM study revealed no difference in the detection of bone lesions at diagnosis when comparing PET/CT and MRI with the former being positive in 95% and the latter in 91% of the patients [12].

Interestingly, there is a lack of studies regarding the comparison of 18F-FDG PET/CT with whole-body CT. According to the recently published consensus statement by the IMWG, although whole-body low-dose CT is the preferred method for the detection of lytic bone lesions in MM, 18F-FDG PET/CT should be considered as a valuable option, because of its ability to identify lytic lesions and extramedullary masses. Moreover, in cases of WBXR-negativity and whole-body MRI-unavailability, 18F-FDG PET/CT is recommended for the differentiation between active and smoldering MM [7].

Further, the newly emerging, hybrid PET/MRI technique seems highly attractive in the diagnostic approach of MM since it combines two modalities with a high potential in myeloma evaluation in a single exam. The results of the only prospective study comparing PET/CT with PET/MRI demonstrated good image quality provided by PET/MRI and high correlation between the modalities regarding the number of detected active lesions and SUV values [14]. However, further studies are warranted to evaluate the potential role of this novel technique in the diagnostics and management of MM.
