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Research ArticleOncology

Clinical Translation of a 68Ga-Labeled Integrin αvβ6–Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer

Xun Feng, Yanpu Wang, Dehua Lu, Xiaoxia Xu, Xin Zhou, Huiyuan Zhang, Ting Zhang, Hua Zhu, Zhi Yang, Fan Wang, Nan Li and Zhaofei Liu
Journal of Nuclear Medicine October 2020, 61 (10) 1461-1467; DOI: https://doi.org/10.2967/jnumed.119.237347
Xun Feng
1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; and
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Yanpu Wang
1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; and
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Dehua Lu
1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; and
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Xiaoxia Xu
2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China
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Xin Zhou
2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China
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Huiyuan Zhang
2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China
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Ting Zhang
1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; and
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Hua Zhu
2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China
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Zhi Yang
2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China
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Fan Wang
1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; and
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Nan Li
2Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Nuclear Medicine, Peking University Cancer Hospital and Institute, Beijing, China
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Zhaofei Liu
1Medical Isotopes Research Center and Department of Radiation Medicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, China; and
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Abstract

The overexpression of integrin αvβ6 in pancreatic cancer makes it a promising target for noninvasive PET imaging. However, currently, most integrin αvβ6–targeting radiotracers are based on linear peptides, which are quickly degraded in the serum by proteinases. Herein, we aimed to develop and assess a 68Ga-labeled integrin αvβ6–targeting cyclic peptide (68Ga-cycratide) for PET imaging of pancreatic cancer. Methods: 68Ga-cycratide was prepared, and its PET imaging profile was compared with that of the linear peptide (68Ga-linear-pep) in an integrin αvβ6–positive BxPC-3 human pancreatic cancer mouse model. Five healthy volunteers (2 women and 3 men) underwent whole-body PET/CT imaging after injection of 68Ga-cycratide, and biodistribution and dosimetry were calculated. PET/CT imaging of 2 patients was performed to investigate the potential role of 68Ga-cycratide in pancreatic cancer diagnosis and treatment monitoring. Results: 68Ga-cycratide exhibited significantly higher tumor uptake than did 68Ga-linear-pep in BxPC-3 tumor–bearing mice, owing—at least in part—to markedly improved in vivo stability. 68Ga-cycratide could sensitively detect the pancreatic cancer lesions in an orthotopic mouse model and was well tolerated in all healthy volunteers. Preliminary PET/CT imaging in patients with pancreatic cancer demonstrated that 68Ga-cycratide was comparable to 18F-FDG for diagnostic imaging and postsurgery tumor relapse monitoring. Conclusion: 68Ga-cycratide is an integrin αvβ6–specific PET radiotracer with favorable pharmacokinetics and a favorable dosimetry profile. 68Ga-cycratide is expected to provide an effective noninvasive PET strategy for pancreatic cancer lesion detection and therapy response monitoring.

  • pancreatic cancer
  • integrin αvβ6
  • 68Ga radiotracer
  • PET/CT
  • cycratide

Footnotes

  • Published online Feb. 21, 2020.

  • © 2020 by the Society of Nuclear Medicine and Molecular Imaging.
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Journal of Nuclear Medicine: 61 (10)
Journal of Nuclear Medicine
Vol. 61, Issue 10
October 1, 2020
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Clinical Translation of a 68Ga-Labeled Integrin αvβ6–Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer
Xun Feng, Yanpu Wang, Dehua Lu, Xiaoxia Xu, Xin Zhou, Huiyuan Zhang, Ting Zhang, Hua Zhu, Zhi Yang, Fan Wang, Nan Li, Zhaofei Liu
Journal of Nuclear Medicine Oct 2020, 61 (10) 1461-1467; DOI: 10.2967/jnumed.119.237347

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Clinical Translation of a 68Ga-Labeled Integrin αvβ6–Targeting Cyclic Radiotracer for PET Imaging of Pancreatic Cancer
Xun Feng, Yanpu Wang, Dehua Lu, Xiaoxia Xu, Xin Zhou, Huiyuan Zhang, Ting Zhang, Hua Zhu, Zhi Yang, Fan Wang, Nan Li, Zhaofei Liu
Journal of Nuclear Medicine Oct 2020, 61 (10) 1461-1467; DOI: 10.2967/jnumed.119.237347
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Keywords

  • pancreatic cancer
  • integrin αvβ6
  • 68Ga radiotracer
  • PET/CT
  • cycratide
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