Tumour visualisation using 18F-fluoro-deoxyglucose (FDG)

Positron emission tomography using FDG

Glucose is essential for providing the energy needed to support cellular processes and is in high demand by areas of the body, which are especially active, such as the brain. Similarly, rapidly growing and differentiating cancer cells have an increased metabolic demand and glucose uptake.

Shutterstock / Molekuul.be

A radiolabelled glucose analogue, 18F-fluoro-deoxyglucose (FDG), is taken up by energy-hungry cancer cells as if it were ordinary glucose. However, the hydroxyl group needed for the glucose to be further metabolised within the cell has been replaced with the radiolabel. Furthermore, phosphorylation of the FDG once it enters the cell means it cannot leave. The FDG is thus trapped within the cell until radioactive decay occurs and a new hydroxyl group is formed allowing the glucose to be metabolized.

The radioactivity elimination half-life of fluorine-18 is 110 minutes, giving adequate time for the trapped 18F-FDG to be visualized using positron emission tomography (PET). In this way, FDG-PET highlights areas of high glucose uptake within the body and can be used for the diagnosis, staging, and monitoring of cancers, particularly Hodgkin's disease, non-Hodgkin's lymphoma, colorectal cancer, breast cancer, melanoma, and lung cancer.1

Quantification of FDG uptake

In addition to visualization of the tumour, it is also useful to quantify the amount of glucose uptake. For example, a treatment may reduce the metabolic rate and growth potential of a tumour without necessarily causing a reduction in size. Although PET scanners are designed to measure the in vivo radioactivity concentration, it is the relative tissue uptake of FDG that is clinically valuable. This is expressed as the standardized uptake value (SUV).

There are several methods for estimating SUVs, but all are subject to significant variability due to physical and biological sources of error, as well as inconsistent image processing and analysis.2 A key factor hampering SUV determination is renal excretion.

Although most FDG is metabolised, around 20% is eliminated by the kidneys. Normally there is minimal glucose in urine as it is reabsorbed by kidney tubules. However, such absorption does not generally happen with FDG so it is excreted in urine. This results in the renal system and bladder being prominent in a normal PET scan.

Novel methodologies for determining FDG excretion

A recent micro-PET study in mice has been used to develop a novel compartmental model and a numerical calculation to describe the excretion of FDG in the renal system. 3 Simultaneous scanning of the entire mouse allowed the amount of the tracer entering the bladder to be determined. FDG-PET data were collected for 12 healthy, untreated mice and 12 healthy mice who had been treated with metformin (a drug that reduces blood glucose concentration without causing hypoglycaemia). The derived model accounts for variations in FDG concentration due to water re-absorption in the renal tubules and increases in bladder volume. Glomerular filtration was found to be the major determinant of tracer elimination and the only stage affected by metformin was the transfer of FDG back to the interstitial space. Calculations using the maximum likelihood approach were found to accurately describe tracer kinetic parameters. Thus this novel approach allows the quantitative estimation of the reduction of FDG de-phosphorylation induced by metformin.

The novel computational tool described here will facilitate the analysis of FDG kinetic response to drug interventions. This will be particularly useful for FDG-PET analysis of tumours in patients with diabetes, which are currently problematic since glucose (and therefore FDG) uptake is limited and results in high levels of radiolabel remaining in the blood. Increasing urinary FDG loss may therefore improve image quality in diabetic patients requiring PET scans for cancer studies.

Micro-PET technology

The full-body mice PET scans in this research were achieved using the Albira preclinical micro-PET system.4 Albira combines PET, SPECT and CT imaging to provide quantitative 3D tomographic imaging of radiotracers, bone, and soft tissue. Through the use of continuous crystals, it corrects for parallax error without sacrificing sensitivity. Albira provides the advanced imaging techniques needed to study dynamic biological process within living animals and provide greater understanding of biological mechanisms and assess the effectiveness of new therapeutics

Positron emission tomography using FDG

Glucose is essential for providing the energy needed to support cellular processes and is in high demand by areas of the body, which are especially active, such as the brain. Similarly, rapidly growing and differentiating cancer cells have an increased metabolic demand and glucose uptake.

A radiolabelled glucose analogue, 18F-fluoro-deoxyglucose (FDG), is taken up by energy-hungry cancer cells as if it were ordinary glucose. However, the hydroxyl group needed for the glucose to be further metabolised within the cell has been replaced with the radiolabel. Furthermore, phosphorylation of the FDG once it enters the cell means it cannot leave. The FDG is thus trapped within the cell until radioactive decay occurs and a new hydroxyl group is formed allowing the glucose to be metabolized.

The radioactivity elimination half-life of fluorine-18 is 110 minutes, giving adequate time for the trapped 18F-FDG to be visualized using positron emission tomography (PET). In this way, FDG-PET highlights areas of high glucose uptake within the body and can be used for the diagnosis, staging, and monitoring of cancers, particularly Hodgkin's disease, non-Hodgkin's lymphoma, colorectal cancer, breast cancer, melanoma, and lung cancer.

Shutterstock / Molekuul.be

Quantification of FDG uptake

In addition to visualization of the tumour, it is also useful to quantify the amount of glucose uptake. For example, a treatment may reduce the metabolic rate and growth potential of a tumour without necessarily causing a reduction in size. Although PET scanners are designed to measure the in vivo radioactivity concentration, it is the relative tissue uptake of FDG that is clinically valuable. This is expressed as the standardized uptake value (SUV).

There are several methods for estimating SUVs, but all are subject to significant variability due to physical and biological sources of error, as well as inconsistent image processing and analysis.2 A key factor hampering SUV determination is renal excretion.

Although most FDG is metabolised, around 20% is eliminated by the kidneys. Normally there is minimal glucose in urine as it is reabsorbed by kidney tubules. However, such absorption does not generally happen with FDG so it is excreted in urine. This results in the renal system and bladder being prominent in a normal PET scan.

Novel methodologies for determining FDG excretion

A recent micro-PET study in mice has been used to develop a novel compartmental model and a numerical calculation to describe the excretion of FDG in the renal system. 3 Simultaneous scanning of the entire mouse allowed the amount of the tracer entering the bladder to be determined. FDG-PET data were collected for 12 healthy, untreated mice and 12 healthy mice who had been treated with metformin (a drug that reduces blood glucose concentration without causing hypoglycaemia). The derived model accounts for variations in FDG concentration due to water re-absorption in the renal tubules and increases in bladder volume. Glomerular filtration was found to be the major determinant of tracer elimination and the only stage affected by metformin was the transfer of FDG back to the interstitial space. Calculations using the maximum likelihood approach were found to accurately describe tracer kinetic parameters. Thus this novel approach allows the quantitative estimation of the reduction of FDG de-phosphorylation induced by metformin.

The novel computational tool described here will facilitate the analysis of FDG kinetic response to drug interventions. This will be particularly useful for FDG-PET analysis of tumours in patients with diabetes, which are currently problematic since glucose (and therefore FDG) uptake is limited and results in high levels of radiolabel remaining in the blood. Increasing urinary FDG loss may therefore improve image quality in diabetic patients requiring PET scans for cancer studies.

References

  1. Kelloff GJ, et al. Progress and Promise of FDG-PET Imaging for Cancer Patient Management and Oncologic Drug Development. Clin Cancer Res 2005;11:2785–2808.
  2. Kinahan PE, Fletcher JW. PET/CT Standardized Uptake Values (SUVs) in Clinical Practice and Assessing Response to Therapy. Semin Ultrasound CT MR. 2010;31(6):496–505.
  3. Garbarino S, et al. A novel description of FDG excretion in the renal system: application to metformin-treated models. Phys. Med. Biol. 2014;59:2469–2484.
  4. Bruker Albira overview. Available at https://www.news-medical.net/ads/abmc.aspx?b=839
  5. https://www.bruker.com/products/mr/preclinical-mri/biospec/overview.html

About Bruker

Bruker is market leader in analytical magnetic resonance instruments including NMR, EPR and preclinical magnetic resonance imaging (MRI). Bruker's product portfolio in the field of magnetic resonance includes NMR, preclinical MRI ,EPR and Time-Domain (TD) NMR. In addition.

Bruker delivers the world's most comprehensive range of research tools enabling life science, materials science, analytical chemistry, process control and clinical research. Bruker is also the leading superconductor magnet and ultra high field magnet manufacturer for NMR and MRI solutions.


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Last updated: May 19, 2015 at 10:16 AM

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