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Molecular Imaging and Biology
Published in: Molecular Imaging and Biology 5/2019

01-10-2019 | Positron Emission Tomography | Research Article

(2S,4R)-4-[18F]Fluoroglutamine as a PET Indicator for Bone Marrow Metabolism Dysfunctional: from Animal Experiments to Clinical Application

Authors: Hua Zhu, Fei Liu, Yan Zhang, Jianhua Yang, Xiaoxia Xu, Xiaoyi Guo, Teli Liu, Nan Li, Lin Zhu, Hank F. Kung, Zhi Yang

Published in: Molecular Imaging and Biology | Issue 5/2019

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Abstract

Purpose

Previous reports confirmed that (2S,4R)-4-[18F]Fluoroglutamine ([18F]GLN) accumulated in bone and bone marrow. This study investigates the potential of using [18F]GLN positron emission tomography (PET) to monitor changes of bone marrow activity after chemotherapy (myelosuppression).

Procedures

Bone marrow inhibition model in mice was induced by an intravenous injection of chemotherapy drug (doxorubicin or rituximab) and the inhibition was confirmed by routine blood cell counts. Bone uptakes of these four radiotracers (2-deoxy-2-[18F]fluoro-D-glucose, [18F]GLN, 3′-dexoy-3′-[18F]fluorothymidine ([18F]FLT), and sodium [18F]fluoride) in the mice were measured after i.v. injection and dissection of femur and tibia, and the uptakes in bone-only (BO) and bone marrow (BM) were obtained after separating bone from bone marrow. Additionally, six volunteers were recruited and evaluated with [18F]GLN. The PET-/CT-guided volumes of interests (VOI) in cervical, thoracic, lumbar vertebra, and skull cortical bone were defined as bone marrow or bone for evaluation, respectively.

Results

[18F]GLN showed a relatively high bone marrow uptake in mice (up to 9.5 ± 1.3 % ID/g) at 1 h after injection, which was 2.1 times that of [18F]FLT. The [18F]GLN uptakes in the bone marrow were substantially inhibited by chemotherapy drug. The decrease of [18F]GLN’s bone marrow uptake was consistent with the reduction of white blood cells (myelosuppression). For [18F]GLN/PET imaging in humans, the SUVmean value of bone marrow (1 h after i.v. injection) was between 3.1 and 3.6 in the healthy volunteers (n = 3), and between 1.8 and 2.2 (n = 3) (P < 0.001) in myelosuppression patients, showing a clear reduction of bone marrow uptake.

Conclusions

Dissection experiments in mice showed that [18F]GLN displayed relatively high bone marrow uptake, and the uptake was sensitive to bone marrow inhibition induced by doxorubicin/rituximab. The same conclusion was confirmed [18F]GLN/PET imaging in humans. Therefore, [18F]GLN/PET imaging may be a useful tool to assess reduction of bone marrow activity in cancer patients, who may be at risk of myelosuppression after chemotherapy.

Trial Registration

Approved by Institutional Review Board of Peking University Cancer Hospital (No. 2017KT38). Registered 18 August 2017.
Appendix
Available only for authorised users
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Metadata
Title
(2S,4R)-4-[18F]Fluoroglutamine as a PET Indicator for Bone Marrow Metabolism Dysfunctional: from Animal Experiments to Clinical Application
Authors
Hua Zhu
Fei Liu
Yan Zhang
Jianhua Yang
Xiaoxia Xu
Xiaoyi Guo
Teli Liu
Nan Li
Lin Zhu
Hank F. Kung
Zhi Yang
Publication date
01-10-2019
Publisher
Springer International Publishing
Published in
Molecular Imaging and Biology / Issue 5/2019
Print ISSN: 1536-1632
Electronic ISSN: 1860-2002
DOI
https://doi.org/10.1007/s11307-019-01319-4

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