Low expression of hexokinase-2 is associated with false-negative FDG–positron emission tomography in multiple myeloma

Rasche, Leo; Angtuaco, Edgardo J.; McDonald, James E.; Buros, Amy; Stein, Caleb K.; Pawlyn, Charlotte; Thanendrarajan, Sharmilan; Schinke, Carolina; Samant, Rohan; Yaccoby, Shmuel; Walker, Brian A.; Epstein, Joshua; Zangari, Maurizio; Rhee, Frits van; Meißner, Tobias; Goldschmidt, Hartmut; Hemminki, Kari; Houlston, Richard S.; Barlogie, Bart; Davies, Faith E.; Morgan, Gareth J.; Weinhold, Niels

doi:10.1182/blood-2017-03-774422

Cited by 193 publications

(147 citation statements)

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“…Whole-body MRI including DW MRI has become established as the most sensitive technique for bone marrow imaging (23)(24)(25) with additional benefits of speed, coverage, and quantification in comparison with traditional MRI, obviating intravenous injections and radiation exposure. Wide anatomic coverage is essential because 50% of lesions would be missed by imaging the spine alone (33).…”

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confidence: 99%

“…Gene expression profiling has revealed lower expression of hexokinase 2, which is involved in the glycolysis pathway, in lesions that are negative at FDG PET and positive at MRI. The prognostic significance of lesions that are discrepant between MRI and FDG PET/CT is not yet known (25). However, whole-body MRI does result in the largest rise in quality-adjusted life years compared with CT or FDG PET/CT (26).…”

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confidence: 99%

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Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma: Myeloma Response Assessment and Diagnosis System (MY-RADS)

Messiou¹,

Hillengaß²,

Delorme³

et al. 2019

Radiology

230

254

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confidence: 99%

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confidence: 99%

Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma: Myeloma Response Assessment and Diagnosis System (MY-RADS)

Messiou¹,

Hillengaß²,

Delorme³

et al. 2019

Radiology

230

254

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“…Moreover, the poor sensitivity for the detection of diffuse bone marrow infiltration or skull lesions, due to masking of their activity by the underlying physiological tracer uptake in the brain, is an important drawback. 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].…”

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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“…In this subset, the gene coding for hexokinase-2, which catalyzes the first step of glycolysis, was expressed significantly less in PET false-negative cases (5.3-fold change, p < 0.001). 28…”

Section: Fdg Pet/ctmentioning

confidence: 99%

Imaging in myeloma with focus on advanced imaging techniques

Barwick

Bretsztajn

Wallitt

et al. 2019

The British Journal of Radiology

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In recent years, there have been major advances in the imaging of myeloma with whole body MRI incorporating diffusion-weighted imaging, emerging as the most sensitive modality. Imaging is now a key component in the work-up of patients with a suspected diagnosis of myeloma. The International Myeloma Working Group now specifies that more than one focal lesion on MRI or lytic lesion on whole body low-dose CT or fludeoxyglucose (FDG) PET/CT fulfil the criteria for bone damage requiring therapy. The recent National Institute for Health and Care Excellence myeloma guidelines recommend imaging in all patients with suspected myeloma. In addition, there is emerging data supporting the use of functional imaging techniques (WB-DW MRI and FDG PET/CT) to predict outcome and evaluate response to therapy. This review summarises the imaging modalities used in myeloma, the latest guidelines relevant to imaging and future directions. 2 of 13 birpublications.org/bjr Br J Radiol;92:20180768 BJR Barwick et al 3 of 13 birpublications.org/bjr Br J Radiol;92:20180768 BJR Review article: Advanced imaging in myeloma

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Low expression of hexokinase-2 is associated with false-negative FDG–positron emission tomography in multiple myeloma

Abstract: Key Points PET false-negativity was seen in 11% of MM patients. PET false-negativity was associated with low hexokinase-2 expression.

Cited by 193 publications

References 20 publications

Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma: Myeloma Response Assessment and Diagnosis System (MY-RADS)

Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma: Myeloma Response Assessment and Diagnosis System (MY-RADS)

Positron Emission Tomography (PET) Radiopharmaceuticals in Multiple Myeloma

Imaging in myeloma with focus on advanced imaging techniques

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