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2-deoxy-2-[18]fluoro-D-glucose PET/CT (18FDG PET/CT) may not be a viable biomarker in Pompe disease.

ABSTRACT: BACKGROUND:Pompe disease (PD) is an autosomal recessive, lysosomal storage disease due to a mutation of the acid ?-glucosidase (GAA) gene. In adult patients, PD is characterized by slowly progressive limb-girdle and trunk myopathy and restrictive respiratory insufficiency. Enzyme replacement therapy (ERT) is available, improving or stabilizing muscle-function in some and slowing deterioration in other patients. Unfortunately, there is no biomarker available to indicate therapeutic efficacy and/or disease activity. Whole body MRI depicts all skeletal muscles demonstrating foci of atrophic muscles, i.e., late and irreversible pathological changes. Any method indicating the localizations of increased muscle glycogen storage, muscle inflammation and/or degradation could possibly help identifying newly afflicted tissue and may be of prognostic value. We therefore investigated 2-deoxy-2-[18]fluoro-D-glucose (FDG) PET, a biomarker for glucose-metabolism, as a tool to evaluate disease activity and prognosis in PD. METHODS:In a pilot study, we investigated four patients by FDG dynamic PET/CT while on ERT. One patient had FDG-PET/CT twice, before and after 12 months on ERT. Dynamic FDG-PET/CT quantifies the metabolic rate of glucose utilisation in mg/ml/min. MRI was performed in parallel with pelvic and thigh muscles semi-quantitatively scored for atrophy and disease-activity. RESULTS:None of the muscles analysed showed a focally increased FDG-uptake. Thus, quantification of muscle glucose metabolism could not be calculated. However, increased FDG-uptake, i.e., increased glucose utilisation, was observed in the respiratory muscles of one patient with severe, restrictive respiratory failure. In contrast, specific MRI sequences showed oedematous as well as atrophic muscle areas in PD. CONCLUSIONS:Our pilot study demonstrates that FDG-uptake does not correlate with glycogen storage in vivo. In contrast, MRI is an excellent tool to demonstrate the extent of muscle involvement. Specific MRI sequences may even demonstrate early changes possibly allowing prognostic predictions or localization of early stages of PD.

SUBMITTER: Plockinger U

PROVIDER: S-EPMC5845361 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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2-deoxy-2-[18]fluoro-D-glucose PET/CT (18FDG PET/CT) may not be a viable biomarker in Pompe disease.

Plöckinger U U Prasad V V Ziagaki A A Tiling N N Poellinger A A

Human genomics 20180309 1

<h4>Background</h4>Pompe disease (PD) is an autosomal recessive, lysosomal storage disease due to a mutation of the acid α-glucosidase (GAA) gene. In adult patients, PD is characterized by slowly progressive limb-girdle and trunk myopathy and restrictive respiratory insufficiency. Enzyme replacement therapy (ERT) is available, improving or stabilizing muscle-function in some and slowing deterioration in other patients. Unfortunately, there is no biomarker available to indicate therapeutic effica ...[more]

PMID: 29523196

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Project description:PurposeThe three positron emission tomography (PET) imaging compounds: (2S,4R)-4-[18F]Fluoroglutamine ([18F]FGln), L-[methyl-11C]Methionine ([11C]Met), and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) were investigated to contrast their ability to image orthotopic BT4C gliomas in BDIX rats. Two separate small animal imaging systems were compared for their tumor detection potential. Dynamic acquisition of [18F]FGln was evaluated with multiple pharmacokinetic models for future quantitative comparison.ProceduresUp to four imaging studies were performed on each orthotopically grafted BT4C glioma-bearing BDIX rat subject (n = 16) on four consecutive days. First, a DOTAREM® contrast enhanced MRI followed by attenuation correction CT and dynamic PET imaging with each radiopharmaceutical (20 min [11C]Met, 60 min [18F]FDG, and 60 min [18F]FGln with either the Molecubes PET/CT (n = 5) or Inveon PET/CT cameras (n = 11). Ex vivo brain autoradiography was completed for each radiopharmaceutical and [18F]FGln pharmacokinetics were studied by injecting 40 MBq into healthy BDIX rats (n = 10) and collecting blood samples between 5 and 60 min. Erythrocyte uptake, plasma protein binding and plasma parent-fraction were combined to estimate the total blood bioavailability of [18F]FGln over time. The corrected PET-image blood data was then applied to multiple pharmacokinetic models.ResultsAverage BT4C tumor-to-healthy brain tissue uptake ratios (TBR) for PET images reached maxima of: [18F]FGln TBR: 1.99 ± 0.19 (n = 13), [18F]FDG TBR: 1.41 ± 0.11 (n = 6), and [11C]Met TBR: 1.08 ± 0.08, (n = 12) for the dynamic PET images. Pharmacokinetic modeling in dynamic [18F]FGln studies suggested both reversible and irreversible uptake play a similar role. Imaging with Inveon and Molecubes yielded similar end-result ratios with insignificant differences (p > 0.25).ConclusionsIn orthotopic BT4C gliomas, [18F]FGln may offer improved imaging versus [11C]Met and [18F]FDG. No significant difference in normalized end-result data was found between the Inveon and Molecubes camera systems. Kinetic modelling of [18F]FGln uptake suggests that both reversible and irreversible uptake play an important role in BDIX rat pharmacokinetics.

Project description:BackgroundSkeletal muscle glucose utilization is an important component of whole-body glucose consumption in normal humans. Fluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) is a non-invasive molecular imaging probe for evaluating tissue glucose utilization. It remains unclear whether or not 18 F-FDG uptake by skeletal muscle has utility as a biomarker for metabolic derangement. We investigated the utility of measurement of muscle 18 F-FDG positron emission tomography/computed tomography uptake as a surrogate marker for existing and incipient metabolic abnormalities.MethodsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptakes of insulin-sensitive organs (liver, pancreas, mesenteric visceral fat, psoas muscle, and abdominal subcutaneous fat) and their association with metabolic abnormalities were evaluated in an experimental group comprising 91 men and 66 women (mean age 49.9 ± 11.1 years). In this cross-sectional cohort, we assessed the predictive power of the optimal cut-off 18 F-FDG uptake [maximum standardized uptake value (SUVmax )]. We confirmed its feasibility and reliability for diagnosis of existing and incipient metabolic derangement in the validation group (longitudinal cohort comprising 91 men and 67 women; mean age 52.6 ± 7.9 years).ResultsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptake (SUVmax ) of psoas muscle was strongly correlated with clinical metabolic parameters in the experimental group. It was positively correlated with waist circumference, body mass index, fasting glucose, triglyceride, systolic and diastolic pressure, and negatively correlated with high-density lipoprotein cholesterol levels (for all, P < 0.05). SUVmax of the psoas muscle also showed the best area under the curve value (0.779) as a predictor of metabolic syndrome (MetS) in the experimental group. Using the optimal cut-off SUVmax of 1.34, the sensitivity, specificity, accuracy, positive, and negative predictive value for predicting existing MetS in the experimental group were 70.0%, 84.6%, 80.9%, 60.9%, and 89.2%, respectively. In the validation group, corresponding values were 47.6%, 92.3%, 86.1%, 50.0%, and 91.6%, respectively. Existing and incipient MetS were significantly higher in subjects with high 18 F-FDG uptake by the psoas muscle (SUVmax > 1.34). Subjects with higher psoas muscle SUVmax had a 3.3-fold increased risk of developing MetS (P = 0.017).ConclusionsFluorine-18-labelled fluoro-2-deoxy-d-glucose (18 F-FDG) uptake of psoas muscle is a promising surrogate marker for existing and incipient metabolic derangement.

Dataset Information

2-deoxy-2-[18]fluoro-D-glucose PET/CT (18FDG PET/CT) may not be a viable biomarker in Pompe disease.

Publications

2-deoxy-2-[18]fluoro-D-glucose PET/CT (18FDG PET/CT) may not be a viable biomarker in Pompe disease.

Similar Datasets

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