Synthesis of [18F]-6-deoxy-6-fluoro-D-glucose ([18F]6FDG), a potential tracer of glucose transport

Neal, T.; Schumann, William C.; Berridge, Marc S.; Landau, Bernard R.

doi:10.1002/jlcr.1003

Cited by 18 publications

(21 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On mornings of the experiments, [ 18 F]6FDG was synthesized using a modification of a previously reported procedure [4,6]. The final product was obtained with purification by HPLC to achieve greater than 99% radiochemical purity.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of metabolism of 6FDG: a PET glucose transport tracer

Muzic

Chandramouli

Huang

et al. 2011

Nuclear Medicine and Biology

View full text Add to dashboard Cite

Introduction-We are developing 18 F-labeled 6-fluoro-6-deoxy-D-glucose ([ 18 F]6FDG) as a tracer of glucose transport. As part of this process it is important to characterize and quantify putative metabolites. In contrast to the ubiquitous PET tracer 18 F-labeled 2-fluoro-2-deoxy-Dglucose ([ 18 F]2FDG) which is phosphorylated and trapped intracellularly, the substitution of fluorine for a hydroxyl group at carbon 6 in [ 18 F]6FDG should prevent its phosphorylation. Consequently, [ 18 F]6FDG has the potential to trace the transport step of glucose metabolism without the confounding effects of phosphorylation and subsequent steps of metabolism. Herein the focus is to determine whether, and the degree to which, [ 18 F]6FDG remains unchanged following intravenous injection.Methods-Biodistribution studies were performed using 6FDG labeled with 18 F as well as the longer-lived radionuclides 3 H and 14 C. Tissues were harvested at 1, 6, and 24 h following intravenous administration and radioactivity was extracted from the tissues and analyzed using a combination of ion exchange columns, high-performance liquid chromatography, and chemical reactivity.Results-At the 1 h time-point, the vast majority of radioactivity in the liver, brain, heart, skeletal muscle, and blood was identified as 6FDG. At the 6-and 24-h time-points there was evidence of a minor amount of radioactive materials that appeared to be 6-fluoro-6-deoxy-Dsorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid. Conclusion-On

show abstract

Section: Methodsmentioning

confidence: 99%

“…We are developing [ 18 F]6-fluoro-6-deoxy-D-glucose ([ 18 F]6FDG) as a glucose analog for imaging only the glucose transport step [4–6]. In addition, when used in conjunction with [ 18 F]2FDG, rates of both the transport and phosphorylation steps can be individually estimated.…”

Section: Introductionmentioning

confidence: 99%

Analysis of metabolism of 6FDG: a PET glucose transport tracer

Muzic

Chandramouli

Huang

et al. 2011

Nuclear Medicine and Biology

View full text Add to dashboard Cite

show abstract

“…[13], in several studies to measure the rate of glucose transport in vivo [14–16]. The advantage of this tracer is that it is transported by GLUTs, although by virtue of its being deoxy at C6, the tracer is not phosphorylated [15].…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone-Induced Insulin Resistance: Kinetic Modeling Using Novel PET Radiopharmaceutical 6-Deoxy-6-[18F]fluoro-d-glucose

Chandramouli

Ismail‐Beigi

et al. 2014

Mol Imaging Biol

View full text Add to dashboard Cite

Purpose An insulin-resistant rat model, induced by dexamethasone, was used to evaluate a Michaelis–Menten-based kinetic model using 6-deoxy-6-[18F]fluoro-D-glucose (6-[18F]FDG) to quantify glucose transport with PET. Procedures Seventeen, male, Sprague–Dawley rats were studied in three groups: control (Ctrl), control+insulin (Ctrl+I), and dexamethasone+insulin (Dex+I). PET scans were acquired for 2 h under euglycemic conditions in the Ctrl group and under hyperinsulinemic-euglycemic conditions in the Ctrl+I and Dex+I groups. Results Glucose transport, assessed according to the 6-[18F]FDG concentration, was highest in skeletal muscle in the Ctrl+I, intermediate in the Dex+I, and lowest in the Ctrl group, while that in the brain was similar among the groups. Modeling analysis applied to the skeletal muscle uptake curves yielded values of parameters related to glucose transport that were greatest in the Ctrl+I group and increased to a lesser degree in the Dex+I group, compared to the Ctrl group. Conclusion 6-[18F]FDG and the Michaelis–Menten-based model can be used to measure insulin-stimulated glucose transport under basal and an insulin resistant state in vivo.

show abstract

“…As detailed in our previous reports (10,18), there has been no success with iodinated and other putative glucose transport tracers that have the potential to be imaged with PET or SPECT. In particular, many of the iodinated glucose derivatives are metabolized, their transport is not responsive to insulin stimulation, or they can only be transported by specific GLUTs.…”

mentioning

confidence: 99%

“…In particular, many of the iodinated glucose derivatives are metabolized, their transport is not responsive to insulin stimulation, or they can only be transported by specific GLUTs. Accordingly, we have pursued the use of 18 F-6FDG as a marker of glucose transport (10,18). The facts that 18 F-6FDG lacks a hydroxyl on carbon-6 and cannot be phosphorylated address the limitation of 18 F-2FDG in tracing transport alone, and the 110-min half-life of the 18 F label helps overcome the disadvantages associated with the short half-life of 11 C-3OMG.…”

mentioning

confidence: 99%

Uptake of ¹⁸F-Labeled 6-Fluoro-6-Deoxy-d-Glucose by Skeletal Muscle Is Responsive to Insulin Stimulation

Spring-Robinson¹,

Chandramouli²,

Schumann³

et al. 2009

J Nucl Med

Self Cite

View full text Add to dashboard Cite

We are developing a methodology for the noninvasive imaging of glucose transport in vivo with PET and 18F-labeled 6-fluoro-6-deoxy-d-glucose (18F-6FDG), a tracer that is transported but not phosphorylated. To validate the method, we evaluated the biodistribution of 18F-6FDG to test whether it is consistent with the known properties of glucose transport, particularly with regard to insulin stimulation of glucose transport. Methods Under glucose clamp conditions, rats were imaged at the baseline and under conditions of hyperinsulinemia. Results The images showed that the radioactivity concentration in skeletal muscle was higher in the presence of insulin than at the baseline. We also found evidence that the metabolism of 18F-6FDG was negligible in several tissues. Conclusion 18F-6FDG is a valid tracer that can be used in in vivo transport studies. PET studies performed under glucose clamp conditions demonstrated that the uptake of nonphosphorylated glucose transport tracer 18F-6FDG is sensitive to insulin stimulation.

show abstract

Synthesis of [18F]-6-deoxy-6-fluoro-D-glucose ([18F]6FDG), a potential tracer of glucose transport

Abstract: SummaryWith the goal of developing a PET radioligand for the in vivo assessment of glucose transport, 6-deoxy-

Cited by 18 publications

References 36 publications

Analysis of metabolism of 6FDG: a PET glucose transport tracer

Analysis of metabolism of 6FDG: a PET glucose transport tracer

Dexamethasone-Induced Insulin Resistance: Kinetic Modeling Using Novel PET Radiopharmaceutical 6-Deoxy-6-[18F]fluoro-d-glucose

Uptake of ¹⁸F-Labeled 6-Fluoro-6-Deoxy-d-Glucose by Skeletal Muscle Is Responsive to Insulin Stimulation

Contact Info

Product

Resources

About

Synthesis of [18F]-6-deoxy-6-fluoro-D-glucose ([18F]6FDG), a potential tracer of glucose transport

Abstract: SummaryWith the goal of developing a PET radioligand for the in vivo assessment of glucose transport, 6-deoxy-

Cited by 18 publications

References 36 publications

Analysis of metabolism of 6FDG: a PET glucose transport tracer

Analysis of metabolism of 6FDG: a PET glucose transport tracer

Dexamethasone-Induced Insulin Resistance: Kinetic Modeling Using Novel PET Radiopharmaceutical 6-Deoxy-6-[18F]fluoro-d-glucose

Uptake of 18F-Labeled 6-Fluoro-6-Deoxy-d-Glucose by Skeletal Muscle Is Responsive to Insulin Stimulation

Contact Info

Product

Resources

About

Uptake of ¹⁸F-Labeled 6-Fluoro-6-Deoxy-d-Glucose by Skeletal Muscle Is Responsive to Insulin Stimulation