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Clinical Research and Public HealthOncology
Open Access | 
10.1172/JCI185408
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Chen, H. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Zhao, L. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Pang, Y. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Shi, J. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Gao, H. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Sun, Y. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Chen, J. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Fu, H. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Cai, J. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Yu, L. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Zeng, R. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Sun, L. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Wu, H. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Wang, Z. in: JCI | PubMed | Google Scholar
1Department of Nuclear Medicine and Minnan PET Center, Xiamen Key Laboratory of Radiopharmaceuticals, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
2Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials, Xiamen Institute of Rare Earth Materials, Haixi Institute, Chinese Academy of Sciences, Xiamen, China.
3Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore.
4Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
5Key Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
6Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen, China.
7Department of Neurosurgery and Department of Neuroscience, Fujian Key Laboratory of Brain Tumors Diagnosis and Precision Treatment, Xiamen Key Laboratory of Brain Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
8Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, International Cancer Institute, Peking University, Beijing, China.
9Guangzhou National Laboratory, Guangzhou, China.
Address correspondence to: Haojun Chen or Zhanxiang Wang, The First Affiliated Hospital of Xiamen University, 55 Zhenhai Road, Xiamen 361003, China. Phone: 86.592.2137077; Email: leochen0821@foxmail.com (HC). Phone: 86.592.2137271; Email: wangzx@xmu.edu.cn (ZW). Or to: Fan Wang, Peking University, 38 Xueyuan Road, Beijing 100191, China. Phone: 86.10.82801145; Email: wangfan@bjmu.edu.cn.
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Find articles by Wang, F. in: JCI | PubMed | Google Scholar
Authorship note: HC, LZ, YP, and JS contributed equally to this work.
Published November 7, 2024 - More info
Published in Volume 135, Issue 1 on January 2, 2025
Abstract
BACKGROUND. Considering that trophoblast cell-surface antigen 2 (Trop2) is overexpressed in a wide range of human epithelial cancers, it presents an attractive target for diagnosis and treatment of multiple types of cancer. Herein, we have developed a Trop2-specific radiotracer, 68Ga-MY6349, and present a prospective, investigator-initiated trial to explore the clinical value of 68Ga-MY6349 PET/CT.
METHODS. In this translational study, 90 patients with 15 types of cancer who underwent 68Ga-MY6349 PET/CT were enrolled prospectively. Among them, 78 patients underwent paired 68Ga-MY6349 and 18F-FDG PET/CT, and 12 patients with prostate cancer underwent paired 68Ga-MY6349 and 68Ga-PSMA-11 PET/CT.
RESULTS. Among the 90 patients across 15 types of cancer, 68Ga-MY6349 uptake in tumors was generally high but heterogeneous, varying among lesions, patients, and cancer types. Trop2 expression level determined by immunohistochemistry was highly correlated with 68Ga-MY6349 uptake at primary and metastatic tumor sites. 68Ga-MY6349 PET/CT showed higher tumor uptake (quantified by maximum standardized uptake value) than 18F-FDG PET/CT in certain types of cancer, including breast (7.2 vs. 5.4, P < 0.001), prostate (9.2 vs. 3.0, P < 0.001), and thyroid cancers (8.5 vs. 3.7, P < 0.001). Compared with 68Ga-PSMA-11, 68Ga-MY6349 PET/CT exhibited comparable lesion uptake (12.2 vs. 12.5, P = 0.223) but a better tumor-to-background contrast (15.8 vs. 12.2, P < 0.001) for primary and metastatic prostate cancer, allowing visualization of more metastatic lesions.
CONCLUSION. 68Ga-MY6349 PET/CT is a noninvasive method for comprehensively assessing Trop2 expression in tumors, which can improve diagnosis and staging for cancer patients and aid in decision making for Trop2-targeted therapies and advancing of personalized treatment.
TRIAL REGISTRATION. ClinicalTrials.gov NCT06188468.
FUNDING. National Natural Science Foundation of China, National Key R&D Program of China, Nuclear Energy R&D project, Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare, Key Scientific Research Program for Young Scholars in Fujian, and Fujian Natural Science Foundation for Distinguished Young Scholars.
Graphical Abstract
Introduction
Trophoblast cell-surface antigen 2 (Trop2), a transmembrane glycoprotein, exhibits high expression in most epithelial cancers and low expression in most normal tissues (1–3). Elevated Trop2 expression is associated with increased tumor cell proliferation and invasion (4), and is correlated with poor prognosis in various cancers (5–7). Thus, Trop2 could be a crucial target for clinical diagnosis and therapeutic intervention in a range of tumors.
Sacituzumab govitecan (SG), an antibody-drug conjugate (ADC) that targets Trop2, has gained US Food and Drug Administration (FDA) approval for use in treating metastatic triple-negative breast cancer (TNBC), hormone receptor–positive breast cancer (HR+ BC), and metastatic urothelial carcinoma (5, 8). Datopotamab deruxtecan, another Trop2-targeting ADC, recently demonstrated encouraging progression-free survival in the phase III TROPION-Lung01 trial for advanced non-squamous non–small cell lung cancer (NSCLC) (9). The phase III ASCENT study (SG versus chemotherapy for metastatic TNBC) suggested that SG efficacy was closely related to Trop2 expression level (10). These data highlight the need for accurate and comprehensive evaluation of Trop2 expression in tumors to stratify patients for precise treatment (11).
The current method for detecting Trop2, based on the immunohistochemical (IHC) staining of biopsy specimens, has limitations due to the temporal and spatial heterogeneity of Trop2 expression in tumors. Noninvasive nuclear medical imaging may overcome these shortcomings and detect changes of Trop2 expression during treatment to guide subsequent therapies.
In this study, we developed a Trop2-specific radiotracer, 68Ga-MY6439, for PET/CT imaging and clinical translation in various cancer types. Although 18F-FDG PET/CT is a standard diagnostic method for tumor imaging in clinical nuclear medicine, it has limitations, including diagnostic sensitivity and specificity. Furthermore, 18F-FDG PET/CT cannot provide information about Trop2 expression in tumors. Therefore, we compared the imaging diagnostic characteristics of 68Ga-MY6349 PET/CT and 18F-FDG PET/CT in different tumors to explore whether 68Ga-MY6349 PET/CT could compensate for some of these shortcomings. Our primary objective was to assess the feasibility of 68Ga-MY6349 PET/CT imaging for the noninvasive assessment of Trop2 expression in various cancer types, promoting precision therapy of Trop2-targeted ADCs, and expand future application. Our secondary objective was to investigate the superiority of 68Ga-MY6349 PET/CT over 18F-FDG PET/CT in some tumors through comparative analysis, providing valuable insights for cancer diagnosis and staging.
ResultsPreparation and preclinical evaluation of 68Ga-MY6439. The Trop2-targeted nanobody MY6349 was modified and radiolabeled with 68Ga, achieving radiochemical purity greater than 95% and specific radioactivity of 146 GBq/μmol (Figure 1A). Stability tests indicated that 68Ga-MY6349 remained stable in PBS and FBS for up to 4 hours, ensuring its suitability for further studies without additional purification (Supplemental Figure 1; supplemental material available online with this article; https://doi.org/10.1172/JCI185408DS1). Regarding the Trop2 expression in the cell lines, BxPC-3 cells had the highest Trop2 expression, followed by HCC1937 and C666-1, with A549 showing negligible expression (Supplemental Figure 2A). Moreover, the colocalization of FITC-MY6349 and full-length Trop2 antibody, observed through flow cytometry and confocal microscopy, validated the specificity of MY6349 to Trop2 (Supplemental Figure 2, B and C). 68Ga-MY6349 exhibited efficient binding to Trop2-positive cell lines, and binding specificity was confirmed by marked binding inhibition in the presence of unlabeled MY6349 and full-length Trop2 antibody, as well as negligible binding to Trop2-negative A549 cells (Supplemental Figure 3). The binding assays demonstrated a high affinity of 68Ga-MY6349 for Trop2, with a 50% inhibitory concentration (IC50) of 1.82 nM and an equilibrium dissociation constant of 11.65 nM (Figure 1, B and C).
Figure 1Preparation and preclinical evaluation of 68Ga-MY6439. (A) The mechanism for radiolabeling MY6349 with 68Ga. RT, room temperature. (B and C) The binding affinity of 68Ga-MY6349 to Trop2, analyzed through half-maximal inhibitory concentration and equilibrium dissociation constant. (D) Representative PET images of 68Ga-MY6349 and blocking experiment in the BxPC-3 tumor model. Yellow arrows, kidneys; green arrows, bladder; white arros, tumor. (E) Quantification results from biodistribution studies of 68Ga-MY6349 with or without the simultaneous injection of unlabeled MY6349. (F) The correlation between PET region of interest (ROI) and biodistribution studies (%ID/g). (G and H) Representative PET images and quantification results of nude mice bearing A549, C666-1, HCC1937, and BxPC-3 tumors at 1 hour after injection, demonstrating Trop2-specific tumoral uptake. The second image in D is shown again as the last image in G. Yellow arrows, kidneys; green arrows, bladder. (I) IHC staining for Trop2 in the corresponding tumors. Scale bar: 100 μm.
Small-animal PET imaging in BxPC-3 tumor xenografts showed rapid tumor accumulation of 68Ga-MY6349 at 0.5 hours after injection (6.3 ± 0.5 percent of the injected dose per gram of tissue [%ID/g]), maintaining sustained level up to 3 hours after injection (6.3 ± 0.8 %ID/g). Coadministration with MY6349 substantially reduced tumor uptake, reconfirming the specificity of 68Ga-MY6349 (Figure 1D). Ex vivo biodistribution studies corroborated these findings (Figure 1E), and the semiquantitative PET data exhibited a strong correlation with the quantitative biodistribution (R2 = 0.9726, P < 0.0001) (Figure 1F). The IHC results were in line with 68Ga-MY6349 PET findings (Figure 1, G–I). These results underscore the capability of 68Ga-MY6349 PET/CT to accurately reflect Trop2 expression in vivo.
Patient characteristics, safety evaluation, and in vivo biodistribution pattern of 68Ga-MY6349. In this clinical translational study conducted between January 2024 and August 2024, 90 patients with 15 cancer types who underwent 68Ga-MY6349 PET/CT were prospectively enrolled (Figure 2). The patient clinical characteristics are shown in Supplemental Table 1. Among the 90 patients, 78 patients underwent paired 68Ga-MY6349 PET/CT and 18F-FDG PET/CT scans. Additionally, 12 patients with prostate cancer underwent paired 68Ga-MY6349 PET/CT and 68Ga-PSMA-11 PET/CT (the standard-of-care imaging for prostate cancer). In this cohort, 45 treatment-naive patients underwent PET/CT for initial tumor staging, and the other 45 patients underwent PET/CT for the identification of tumor recurrence and metastases. Diagnoses were confirmed via pathology (from biopsy or surgery samples) in 67 patients and via imaging and/or clinical follow-up in the remaining 23 patients.
Figure 2Flow diagram outlining the clinical study design and participating patients.
All participants tolerated 68Ga-MY6349 well, with no adverse events reported during injection or the 4-hour follow-up period. Supplemental Figure 4 shows representative PET-MIP (maximum-intensity projection) images at various time points along with biodistribution data in normal organs (for 3 patients). The effective dose of 68Ga-MY6349, calculated using OLINDA/EXM software, was 1.46 × 10−2 m
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