PET/CT in Multiple Myeloma: Beyond FDG

Abstract

Recent advances in the diagnosis and treatment of multiple myeloma (MM) have highlighted the importance of imaging methods, not only in the localization and extent of the disease but also in prognostic stratification and assessment of response to therapy. In this context, PET/CT, combining both morphological and functional information, is particularly useful in this pathology. The tracer mostly used is 18F-FDG, a glucose analog, which provides extremely accurate information with a sensitivity ranging from 80 to 100%. However, this tracer has some limitations, mostly related to the physiological uptake of FDG in the bone marrow and brain, which reduce its effectiveness. For this reason, some studies in the literature have evaluated the effectiveness of other PET tracers, which provide information on protein metabolism or the synthesis of metabolic plasma membranes, such as choline and methionine, as well as innovative radiopharmaceuticals, directed against receptors expressed by cells of myeloma, including tracers directed to the chemokine receptor. This review analyzes the characteristics and accuracy of non-FDG tracers in the management of patients with multiple myeloma.

ChoK-Full of Potential: Choline Kinase in B Cell and T Cell Malignancies

“…More recently, PET/CT imaging studies with [ 11 C]-choline or [ 18 F]-fluorocholine have allowed the detection of DLBCL and Hodgkin lymphoma (HL) in patients with recurrent prostate cancer [ 28 , 44 , 45 ]. PET/CT imaging with [ 11 C]-choline or [ 18 F]-fluorocholine has actually become a useful tool for staging and assessment of therapeutic response in patients with NHL, MM and CNSL, and has demonstrated much higher sensitivity and specificity for MM and CNSL than the widely used [ 18 F]-FDG [ 27 , 29 , 30 , 31 ]. However, the specificity of choline tracers is not absolute, as [ 11 C]-choline or [ 18 F]-fluorocholine is also accumulated in tissues with sterile inflammation and bacterial/viral infections [ 2 , 5 , 46 ].…”

“…Radiolabeled choline tracers are particularly useful for diagnostic imaging of brain tumors, prostate cancer, lung cancer, esophageal cancer and hepatocellular carcinoma, in which the commonly used glucose tracer [ 18 F]-2-fluoro-2-deoxyglucose (FDG) lacks specificity or sensitivity [ 2 , 5 ]. Interestingly, both MRS imaging of tCho and PET/CT imaging with [ 11 C]-choline or [ 18 F]-fluorocholine tracers have also been clinically applied for the diagnosis of lymphoid malignancies, including non-Hodgkin lymphoma (NHL), multiple myeloma (MM) and central nervous system lymphoma (CNSL) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. However, in contrast to the well-documented oncogenic alterations and pathways that cause CHKα overexpression in solid tumors, information on how choline kinase is dysregulated in lymphoid malignancies is very limited and has just begun to be unraveled.…”

Metabolic Volume Measurements in Multiple Myeloma

“…It seems to have greater positivity than FDG in MM [74]. Old PET tracers such as 11C-choline and 11C-methionine have also been used to study MM [75]. Choline is a component of phosphatidylcholine; therefore, 11C-choline is an indicator of plasma membrane synthesis.…”

“…Choline is a component of phosphatidylcholine; therefore, 11C-choline is an indicator of plasma membrane synthesis. The radiolabeled amino acid methionine is supposed to be rapidly incorporated into newly synthesized immunoglobulins in MM lesions [75].…”

“…It is interesting and intriguing that radiopharmaceuticals that represent such diverse metabolic aspects can identify the same disease. Generally, different tracers present different uptake intensities in different lesions of the same MM patient [71,74,75]. The entirely distinct uptake mechanisms of these radiopharmaceuticals suggest that this is related to the very heterogeneous biological behavior of this disease.…”