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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 4/2020

Open Access 01-08-2020 | Glioma | Research Article

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

Authors: Maxwell WG Miner, Heidi Liljenbäck, Jenni Virta, Joni Merisaari, Vesa Oikonen, Jukka Westermarck, Xiang-Guo Li, Anne Roivainen

Published in: Molecular Imaging and Biology | Issue 4/2020

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Abstract

Purpose

The glutamine analogue (2S, 4R)-4-[18F]fluoroglutamine ([18F]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

[18F]FGln was synthesized at a high radiochemical purity as analyzed by high-performance liquid chromatography. An orthotopic model was created by injecting luciferase-expressing patient-derived BT3 glioma cells into the right hemisphere of BALB/cOlaHsd-Foxn1nu 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 Foxn1nu/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 Foxn1nu/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 whole-blood 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 [18F]FGln has preferential uptake in glioma tissue versus that of corresponding healthy tissue and fits well with reversible uptake models.
Appendix
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Metadata
Title
(2S, 4R)-4-[18F]Fluoroglutamine for In vivo PET Imaging of Glioma Xenografts in Mice: an Evaluation of Multiple Pharmacokinetic Models
Authors
Maxwell WG Miner
Heidi Liljenbäck
Jenni Virta
Joni Merisaari
Vesa Oikonen
Jukka Westermarck
Xiang-Guo Li
Anne Roivainen
Publication date
01-08-2020
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 4/2020
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-020-01472-1

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