*3.4. 18F-Fluorothymidine (18F-FLT)*

18F-Fluorothymidine (18F-FLT) is the most studied cellular proliferation PET agent [54]. 18F-FLT is taken up by cells and phosphorylated by thymidine kinase 1, which is upregulated by about tenfold during the S-phase of the cell cycle, producing 18F-FLT monophosphate (18F-FLT-MP), which can then be sequentially phosphorylated to form 18F-FLT diphosphate (18F-FLT-DP) and 18F-FLT triphosphate ( 18F-FLT-TP). These phosphorylated products are metabolically trapped intracellularly without being incorporated into DNA. The tracer retention within cells reflects, in part, thymidine kinase activity and is often positively correlated with cellular proliferation [55].

The knowledge regarding application and performance of 18F-FLT PET in MM is limited. Agool et al. studied a group of 18 patients with different hematologic disorders, among which were two patients with MM. The authors found that the affected osteolytic areas in these two MM patients demonstrated a low 18F-FLT uptake [56]. In a pilot study on combined 18F-FDG and 18F-FLT PET/CT imaging in 8 myeloma patients (4 patients with symptomatic MM, 4 patients with SMM) the number of myeloma-indicative lesions was significantly higher for 18F-FDG PET/CT than for 18F-FLT

PET/CT. A common finding of the study was a mismatch of focally increased 18F-FDG uptake and reduced 18F-FLT uptake (lower than the surrounding bone marrow) in myeloma lesions. Moreover, 18F-FLT PET/CT was characterized by high background activity in the bone marrow compartment, complicating the evaluation of bone marrow lesions [57].

In conclusion, despite the limited number of patients studied so far, the preliminary results indicate that 18F-FLT does not seem suitable as a single PET tracer in MM diagnostics.
