Preclinical study of an 18F-labeled glutamine derivative for cancer imaging

Liu, Cong; Liu, Hui; Duan, Dongban; Zhou, Zhenhan; Liu, Zhibo

doi:10.1016/j.nucmedbio.2018.06.007

Cited by 14 publications

(23 citation statements)

References 35 publications

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“…Although not necessarily the final solution due to the ubiquity of which the native analogue (glutamine) is used throughout the mammalian body, [ 18 F]FGln may represent the next step forward in PET imaging brain cancers due to the particularly low brain basal uptake level providing exceptional tumor tissue contrast [4]. Further variants in structure: alkyl chains [25], poly peptide additions [26], and a boron trifluoride variant [27] are continuously being investigated in search of improvements in imaging and in vivo stability.…”

Section: Introductionmentioning

confidence: 99%

(2S, 4R)-4-[18F]Fluoroglutamine for In vivo PET Imaging of Glioma Xenografts in Mice: an Evaluation of Multiple Pharmacokinetic Models

et al. 2020

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Purpose: The glutamine analogue (2S, 4R)-4-[ 18 F]fluoroglutamine ([ 18 F]FGln) was investigated to further characterize its pharmacokinetics and acquire in vivo positron emission tomography (PET) images of separate orthotopic and subcutaneous glioma xenografts in mice. Procedures: [ 18 F]FGln was synthesized at a high radiochemical purity as analyzed by highperformance liquid chromatography. An orthotopic model was created by injecting luciferaseexpressing patient-derived BT3 glioma cells into the right hemisphere of BALB/cOlaHsd-Foxn1 nu mouse brains (tumor growth monitored via in vivo bioluminescence), the subcutaneous model by injecting rat BT4C glioma cells into the flank and neck regions of Foxn1 nu/nu mice. Dynamic PET images were acquired after injecting 10-12 MBq of the tracer into mouse tail veins. Animals were sacrificed 63 min after tracer injection, and ex vivo biodistributions were measured. Tumors and whole brains (with tumors) were cryosectioned, autoradiographed, and stained with hematoxylin-eosin. All images were analyzed with CARIMAS software. Blood sampling of 6 Foxn1 nu/nu and 6 C57BL/6J mice was performed after 9-14 MBq of tracer was injected at time points between 5 and 60 min then assayed for erythrocyte uptake, plasma protein binding, and plasma parent-fraction of radioactivity to correct PET image-derived wholeblood radioactivity and apply the data to multiple pharmacokinetic models. Results: Orthotopic human glioma xenografts displayed PET image tumor-to-healthy brain region ratio of 3.6 and 4.8 while subcutaneously xenografted BT4C gliomas displayed (n = 12) a tumor-to-muscle (flank) ratio of 1.9 ± 0.7 (range 1.3-3.4). Using PET image-derived blood radioactivity corrected by population-based stability analyses, tumor uptake pharmacokinetics fit Logan and Yokoi modeling for reversible uptake. Conclusions: The results reinforce that [ 18 F]FGln has preferential uptake in glioma tissue versus that of corresponding healthy tissue and fits well with reversible uptake models.

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Section: Introductionmentioning

confidence: 99%

(2S, 4R)-4-[18F]Fluoroglutamine for In vivo PET Imaging of Glioma Xenografts in Mice: an Evaluation of Multiple Pharmacokinetic Models

et al. 2020

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“…This indicates that the conversion from glutamine to glutamate is fast. Several studies using PET have shown that glutamine analogue tracers were taken up by cancer cells rapidly, 28‐31 even faster than 2‐deoxy‐2‐ 18 F‐fluoro‐D‐glucose (FDG). The time scale of the initial uptake is similar to that of glutamine uptake shown in Figures 4 and 5.…”

Section: Discussionmentioning

confidence: 99%

L‐glutamine as a T₂ exchange contrast agent

Joo

Yang

Choi

et al. 2020

Magnetic Resonance in Med

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Purpose The potential of L‐glutamine as a T2 exchange contrast agent in MRI was investigated. Methods The T2 relaxation rate of L‐glutamine solutions prepared in various concentrations was measured at 9.4 T. A series of T2‐weighted images in a mouse cancer model was acquired with an L‐glutamine solution infusion. Results The T2 relaxivity caused by the exchange (R2ex) at 37°C was 0.069 s−1 mM−1 and 0.102 s−1 mM−1 for glutamine and glutamate solutions at pH = 7.2, respectively. The R2ex of glutamine at pH = 6.1–6.7 was in the 0.097–0.1 s−1 mM−1 range. No significant dependence of T1 on the concentration of glutamine was observed. The dynamic measurement of T2‐weighted images in vivo showed that the glutamine uptake was primarily observed at the localized part of the tumor Conclusion L‐glutamine can be used as a T2 exchange contrast agent and images of glutamine uptake in vivo can be acquired.

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“…18 F-Gln-BF 3 is another tracer that has shown significant uptake in xenograft studies (Ref. 129) (Table 1, Fig. 7).…”

Section: Therapeutic Strategies Arising From the Warburg Effect And Amentioning

confidence: 99%

Warburg and Krebs and related effects in cancer

Unterlass

Curtin

2019

Expert Rev. Mol. Med.

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Warburg and coworkers' observation of altered glucose metabolism in tumours has been neglected for several decades, which, in part, was because of an initial misinterpretation of the basis of their finding. Following the realisation that genetic alterations are often linked to metabolism, and that the tumour micro-environment imposes different demands on cancer cells, has led to a reinvestigation of cancer metabolism in recent years. Increasing our understanding of the drivers and consequences of the Warburg effect in cancer and beyond will help to identify new therapeutic strategies as well as to identify new prognostic and therapeutic biomarkers. Here we discuss the initial findings of Warburg and coworkers regarding cancer cell glucose metabolism, how these studies came into focus again in recent years following the discovery of metabolic oncogenes, and the therapeutic potential that lies within targeting the altered metabolic phenotype in cancer. In addition, another essential nutrient in cancer metabolism, glutamine, will be discussed.

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Preclinical study of an 18F-labeled glutamine derivative for cancer imaging

Cited by 14 publications

References 35 publications

(2S, 4R)-4-[18F]Fluoroglutamine for In vivo PET Imaging of Glioma Xenografts in Mice: an Evaluation of Multiple Pharmacokinetic Models

(2S, 4R)-4-[18F]Fluoroglutamine for In vivo PET Imaging of Glioma Xenografts in Mice: an Evaluation of Multiple Pharmacokinetic Models

L‐glutamine as a T₂ exchange contrast agent

Warburg and Krebs and related effects in cancer

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