Dynamic PET/CT imaging of 18F-(2S, 4R)4-fluoroglutamine in healthy volunteers and oncological patients

Xu, Xiaoxia; Zhu, Hua; Liu, Fei; Zhang, Yan; Yang, Jianhua; Zhang, Lifang; Xie, Qing; Zhu, Lin; Li, Nan; Kung, Hank F.; Yang, Zhi

doi:10.1007/s00259-019-04543-w

Cited by 13 publications

(55 citation statements)

References 37 publications

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Section: Introductionmentioning

confidence: 94%

“…In cell uptake studies and early animal data, 18 F-Gln generally washes out from cells over time, suggesting reversible transport (12,20). These properties make 18 F-Gln an ideal radiotracer for measuring glutamine pool size. Indeed, 18 F-Gln tumor-to-blood ratios demonstrated a strong positive correlation with glutamine pool size as measured by 1 H magnetic resonance spectroscopy (12).…”

Section: Introductionmentioning

confidence: 94%

“…Malignant cells reprogram pathways of energy metabolism for accelerated growth (1), providing opportunities for imaging and targeted treatment. Dysregulated glucose metabolism has been leveraged for PET imaging with 18 F-fluorodeoxyglucose ( 18 F-FDG), a tracer that has shown broad clinical applicability, in clinical oncologic imaging (2). A growing body of research suggests that dysregulated cellular metabolism extends beyond that of increased glucose consumption (3).…”

Section: Introductionmentioning

confidence: 99%

“…The PET radiotracer 18 F-(2S,4R)4-Fluoroglutamine ( 18 F-Gln) has been developed as an in vivo measure of tumor glutamine metabolism (15) and uptake has been seen in a variety of cancers (16)(17)(18)(19). 18 F-Gln utilizes the same cellular transporters as native glutamine but is minimally metabolized (12,17,20).…”

Section: Introductionmentioning

confidence: 99%

“…These properties make 18 F-Gln an ideal radiotracer for measuring glutamine pool size. Indeed, 18 F-Gln tumor-to-blood ratios demonstrated a strong positive correlation with glutamine pool size as measured by 1 H magnetic resonance spectroscopy (12). However, the optimal method for PET image analysis has not been established for this experimental radiotracer.…”

Section: Introductionmentioning

confidence: 99%

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Kinetic Modeling of ¹⁸F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism

et al. 2020

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The PET radiotracer 18 F-(2S,4R)4-Fluoroglutamine ( 18 F-Gln) reflects glutamine transport and can be used to infer glutamine metabolism. Mouse xenograft studies have demonstrated that 18 F-Gln uptake correlates directly with glutamine pool size and is inversely related to glutamine metabolism through the glutaminase enzyme. To provide a framework for the analysis of 18 F-Gln-PET, we have examined 18 F-Gln uptake kinetics in mouse models of breast cancer at baseline and after inhibition of glutaminase. We describe results of the pre-clinical analysis and computer simulations with the goal of model validation and performance assessment in anticipation of human breast cancer patient studies. Methods: Triplenegative breast cancer and receptor-positive xenografts were implanted in athymic mice. PET mouse imaging was performed at baseline and after treatment with a glutaminase inhibitor or a vehicle solution for a total of four mouse groups. Dynamic PET images were obtained for one hour beginning at the time of intravenous injection of 18 F-FGln. Kinetic analysis and computer simulations were performed on a representative time-activity curves (TAC), testing 1-and 2-compartment models to describe kinetics.Results: Dynamic imaging for one hour captured blood and tumor TACs indicative of largely reversible uptake of 18 F-FGln in tumors. Consistent with this observation, a two-compartment model indicated a relatively low estimate of trapping (k 3 ) , suggesting that the one-compartment model is preferable. Logan plot graphical analysis demonstrated late linearity, supporting reversible kinetics and modeling with a single compartment. Analysis of the mouse data and simulations suggests that estimates of glutamine pools size, specifically the V D for 18 F-FGln, were more reliably estimated using the one-compartment reversible model compared to the two-compartment irreversible model. Tumor-to-blood ratios, a more practical potential proxy of V D , demonstrated good correlation with volume of distribution from singlecompartment models and Logan analyses. Conclusions: Kinetic analysis of dynamic 18 F-Gln-PET images demonstrated the ability to measure V D to estimate glutamine pool size, a key indicator of cellular glutamine metabolism, by both a one-compartment model and Logan analysis. Changes in V D with glutaminase inhibition supports the ability to assess response to glutamine metabolism-targeted therapy.Concordance of kinetic measures with tumor-to-blood ratios provides a clinically feasible approach for human imaging.

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Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Kinetic Modeling of ¹⁸F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism

et al. 2020

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Molecular Imaging Platform and Radiopharmaceutical Translational Research on Peking University Cancer Hospital

Yang,

Meng,

Guo

et al. 2024

Beyond Becquerel and Biology to Precision Radiomolecular Oncology: Festschrift in Honor of Richard P. Baum

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On August 27, 2019, the signing ceremony for the cooperation between Peking University Cancer Hospital (PKUCH) and the International Centers for Precision Oncology (ICPO) was held successfully in the scientific research building of PKUCH-NM. The research interests of the PKUCH-NM include nuclear medicine clinical research, as well as the development of multimodality/multiplexed molecular probes for tumor diagnosis and therapy.

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Evaluation of (2S,4S)-4-[¹⁸F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging

Huang,

Liu,

et al. 2023

Mol. Pharmaceutics

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Dynamic PET/CT imaging of 18F-(2S, 4R)4-fluoroglutamine in healthy volunteers and oncological patients

Cited by 13 publications

References 37 publications

Kinetic Modeling of ¹⁸F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism

Kinetic Modeling of ¹⁸F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism

Molecular Imaging Platform and Radiopharmaceutical Translational Research on Peking University Cancer Hospital

Evaluation of (2S,4S)-4-[¹⁸F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging

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Dynamic PET/CT imaging of 18F-(2S, 4R)4-fluoroglutamine in healthy volunteers and oncological patients

Cited by 13 publications

References 37 publications

Kinetic Modeling of 18F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism

Kinetic Modeling of 18F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism

Molecular Imaging Platform and Radiopharmaceutical Translational Research on Peking University Cancer Hospital

Evaluation of (2S,4S)-4-[18F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging

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Product

Resources

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Kinetic Modeling of ¹⁸F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism

Kinetic Modeling of ¹⁸F-(2S,4R)4-Fluoroglutamine in Mouse Models of Breast Cancer to Estimate Glutamine Pool Size as an Indicator of Tumor Glutamine Metabolism

Evaluation of (2S,4S)-4-[¹⁸F]FEBGln as a Positron Emission Tomography Tracer for Tumor Imaging