Nuclear medicine imaging of multiple myeloma, particularly in the relapsed setting

Abstract

Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity. Modern imaging techniques such as magnetic resonance imaging, positron emission tomography and computed tomography offer superior detection of myeloma bone disease and extramedullary manifestations. In particular, the properties of nuclear imaging enable the identification of disease activity by directly targeting the specific cellular properties of malignant plasma cells. In this review, an overview is provided of the effectiveness of radiopharmaceuticals that target metabolism, surface receptors and angiogenesis. The available literature data for commonly used nuclear imaging tracers, the promising first results of new tracers, and our pilot work indicate that a number of these radiopharmaceutical applications can be used effectively for staging and response monitoring of relapsing MM patients. Moreover, some tracers can potentially be used for radio immunotherapy.

ImmunoPET imaging of CD38 in murine lymphoma models using 89Zr-labeled daratumumab

“…18 F-FDG PET/CT has limitations including a lack of sensitivity for detecting diffuse bone marrow involvement, low-density plasmocyte infiltration, as well as some small skull lesions [23]. Other PET tracers have been developed that might be useful in the workup of patients with newly diagnosed and relapsing MM, including 11 C-MET for protein synthesis, 3’-deoxy-3’- 18 F-fluorothymidine ( 18 F-FLT) for DNA synthesis, 11 C-acetate for amino acids synthesis, and so forth [24]. Although CD38 is considered a standard biomarker for immunophenotypic identification of MM [6, 11], clinical CD38 detection in bone marrow or extramedullary lesions can only be done using immunophenotypic or PCR-based molecular techniques [25].…”

Agreement Between 18F-FDG PET/CT and Whole-Body Magnetic Resonance Compared With Skeletal Survey for Initial Staging and Response at End-of-Treatment Evaluation of Patients With Multiple Myeloma

“…Recent studies incorporate very promising new radiopharmaceuticals such as 11 C-methionine, with a diagnostic superiority over 18 F-FDG in MM, with a good correlation between radiotracer uptake and bone marrow involvement, 21 as 18 F-FDG evaluates glucose consumption, whereas 11 C-methionine depicts protein synthesis. Other tracers are being evaluated in monitoring response to treatment in MM, 19 , 20 although there is still no consensus on their utilization. 4 , 22 Furthermore, a clinical trial compared 2 branches, one with WB-MR and the other with 18 F-FDG PET/CT in 134 patients at initial diagnosis, at interim treatment, monitoring response to therapy, and evaluating the prognosis.…”

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

“…The tracer is actively transported into cells by the glucose transporter proteins (GLUT), which are expressed at a high degree in tumor cells due to their enhanced glucose demands. 18 F-FDG, as a glucose analogue, is taken up by the neoplastic cells, undergoes phosphorylation and then gets trapped intracellularly, since 18 F-FDG is not a substrate for further metabolic processing by either phosphohexose isomerase or glucose-6-phosphate dehydrogenase [6]. 18 F-FDG PET/CT has become nowadays a standard imaging technique in several tumor entities.…”

“…One of the reasons leading to an increased metabolic activity detected with 18 F-FDG PET/CT is tumor hypoxia. Tumor hypoxia leads to enhanced production of several hypoxia inducible factors, resulting in increased microvessel density (MVD) around the malignant plasma cells [6]. MVD has been proven to be correlated with disease progression in MM [87].…”