Hexokinase-2 Expression in <sup>11</sup>C-Methionine–Positive, <sup>18</sup>F-FDG–Negative Multiple Myeloma

Kircher, Stefan; Stolzenburg, Antje; Kortüm, K. Martin; Kircher, Malte; Viá, Matteo Da; Samnick, Samuel; Buck, Andreas K.; Einsele, Hermann; Rosenwald, Andreas; Lapa, Constantin

doi:10.2967/jnumed.118.217539

Cited by 26 publications

(26 citation statements)

References 25 publications

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“…In a report of 227 MM patients the incidence of PET false-negativity was 11% in these patients, a finding attributed to the significantly lower expression of the gene coding for hexokinase-2, which catalyzes the first step of glycolysis [32]. However, this explanation warrants further validation [33]. Further, 18 F-FDG, as a glucose analog, is generally restricted in oncological imaging by both false positive (inflammation, post-surgical areas, recent use of chemotherapy, fractures, etc.)…”

Section: Limitations Of 18 F-fdg Pet/ctmentioning

confidence: 98%

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

Sachpekidis

Goldschmidt

Dimitrakopoulou-Strauß

2019

Molecules

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Multiple myeloma (MM) is a plasma cell disorder, characterized by clonal proliferation of malignant plasma cells in the bone marrow. Bone disease is the most frequent feature and an end-organ defining indicator of MM. In this context, imaging plays a pivotal role in the management of the malignancy. For several decades whole-body X-ray survey (WBXR) has been applied for the diagnosis and staging of bone disease in MM. However, the serious drawbacks of WBXR have led to its gradual replacement from novel imaging modalities, such as computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT). PET/CT, with the tracer 18 F-fluorodeoxyglucose ( 18 F-FDG), is now considered a powerful diagnostic tool for the detection of medullary and extramedullary disease at the time of diagnosis, a reliable predictor of survival as well as the most robust modality for treatment response evaluation in MM. On the other hand, 18 F-FDG carries its own limitations as a radiopharmaceutical, including a rather poor sensitivity for the detection of diffuse bone marrow infiltration, a relatively low specificity, and the lack of widely applied, established criteria for image interpretation. This has led to the development of several alternative PET tracers, some of which with promising results regarding MM detection. The aim of this review article is to outline the major applications of PET/CT with different radiopharmaceuticals in the clinical practice of MM.

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Section: Limitations Of 18 F-fdg Pet/ctmentioning

confidence: 98%

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

Sachpekidis

Goldschmidt

Dimitrakopoulou-Strauß

2019

Molecules

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“…It was recently pointed out that about 10% of newly diagnosed MM patients, with bone lesions on MRI, are FDG-negative, which is linked to a lower expression of hexokinase-2 [19]. Another study showed that newly diagnosed MM patients with false-negative findings on FDG PET/CT had longer PFS than FDG-positive patients [30]; however, other mechanisms also appear to be involved in the uptake as FDG-negative patients with relapsed/refractory disease were found to have normal expression of Hexokinase-2 [31]. Finally, the use of dexamethasone as a treatment option can decrease FDG-uptake by promoting MM cell apoptosis and by lowering the inflammatory environment of MM cells.…”

Section: Uptake Patterns Of 18fdg and Choline-based Tracersmentioning

confidence: 99%

Choline PET/CT in Multiple Myeloma

Mesguich

Hulin

Lascaux

et al. 2020

Cancers

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The field of multiple myeloma (MM) imaging has evolved. The International Myeloma Working Group recently recommended performing 18F-fluorodeoxyglucose glucose (18FDG) positron emission tomography/computed tomography (PET/CT) with the aim of staging MM patients at baseline and evaluating response to therapy. Novel oncological radiotracers such as 11C-Choline and 18F-Fluorocholine, have been studied in comparison with 18FDG, mostly in MM patients presenting with refractory disease or suspected relapse. Choline-based tracers may overcome some limitations of 18FDG, which include a lack of sensitivity in depicting skull lesions and the fact that 10% of MM patients are FDG-negative. The majority of MM lesions display a higher uptake of Choline than FDG. Also, in many situations, Choline may offer better lesion visualization, with a higher tumor to background ratio; however, various patterns of Choline and FDG uptake have been observed in MM and some limitations, notably as regards liver lesions, should be recognized. Overall, Choline may provide additional detection of up to 75% more lesions. This article aims to provide a comprehensive review of the potential role of Choline in multiple myeloma, as compared to FDG, encompassing Choline physiopathology as well as data from clinical studies.

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“…Metallic implants might lead to false positive results, as well as inflammatory states; alternatively, the patients’ hyperglycemia and steroid therapy that transiently suppress the metabolic state can enhance the false-negative rate [43]. Rasche et al found that hexokinase-2-low expression can also reduce the diagnostic sensitivity, due to the FDG phosphorylation decrease and subsequent lower uptake by tumor cells [46,47].…”

Section: Genetic Determinants Of Multiple Myeloma and Clinical Promentioning

confidence: 99%

High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment

Solimando

Viá

Cicco

et al. 2019

JCM

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Multiple myeloma (MM) is a genetically heterogeneous disease that includes a subgroup of 10–15% of patients facing dismal survival despite the most intensive treatment. Despite improvements in biological knowledge, MM is still an incurable neoplasia, and therapeutic options able to overcome the relapsing/refractory behavior represent an unmet clinical need. The aim of this review is to provide an integrated clinical and biological overview of high-risk MM, discussing novel therapeutic perspectives, targeting the neoplastic clone and its microenvironment. The dissection of the molecular determinants of the aggressive phenotypes and drug-resistance can foster a better tailored clinical management of the high-risk profile and therapy-refractoriness. Among the current clinical difficulties in MM, patients’ management by manipulating the tumor niche represents a major challenge. The angiogenesis and the stromal infiltrate constitute pivotal mechanisms of a mutual collaboration between MM and the non-tumoral counterpart. Immuno-modulatory and anti-angiogenic therapy hold great efficacy, but variable and unpredictable responses in high-risk MM. The comprehensive understanding of the genetic heterogeneity and MM high-risk ecosystem enforce a systematic bench-to-bedside approach. Here, we provide a broad outlook of novel druggable targets. We also summarize the existing multi-omics-based risk profiling tools, in order to better select candidates for dual immune/vasculogenesis targeting.

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Hexokinase-2 Expression in ¹¹C-Methionine–Positive, ¹⁸F-FDG–Negative Multiple Myeloma

Cited by 26 publications

References 25 publications

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

Choline PET/CT in Multiple Myeloma

High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment

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Hexokinase-2 Expression in 11C-Methionine–Positive, 18F-FDG–Negative Multiple Myeloma

Cited by 26 publications

References 25 publications

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

Choline PET/CT in Multiple Myeloma

High-Risk Multiple Myeloma: Integrated Clinical and Omics Approach Dissects the Neoplastic Clone and the Tumor Microenvironment

Contact Info

Product

Resources

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Hexokinase-2 Expression in ¹¹C-Methionine–Positive, ¹⁸F-FDG–Negative Multiple Myeloma