Hua Zhu1, Fei Liu1, Yan Zhang2, Jianhua Yang1, Xiaoxia Xu1, Xiaoyi Guo1, Teli Liu1, Nan Li1, Lin Zhu2,3, Hank F Kung4,5, Zhi Yang6. 1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, China. 2. Key Laboratory of Radiopharmaceuticals, Ministry of Education, Beijing Normal University, Beijing, 100875, China. 3. Capital Medical University, Beijing Institute for Brain Diseases, Beijing, 100069, China. 4. Capital Medical University, Beijing Institute for Brain Diseases, Beijing, 100069, China. kunghf@gmail.com. 5. Department of Radiology, University of Pennsylvania School of Medicine, 3700 Market Street, Suite 305, Philadelphia, PA, 19104, USA. kunghf@gmail.com. 6. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital & Institute, Beijing, 100142, China. pekyz@163.com.
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.
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 myelosuppressionpatients, 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 cancerpatients, 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.
Entities:
Keywords:
(2S,4R)-4-[18F]fluoroglutamine; Bone marrow; Glutamine metabolic imaging; Myelosuppression
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