Amino Acids

, Volume 50, Issue 3–4, pp 409–419 | Cite as

Pre-clinical study of a TNFR1-targeted 18F probe for PET imaging of breast cancer

  • Hao Fu
  • Hua Wu
  • Xianzhong Zhang
  • Jinxiong Huang
  • Xiaojiang He
  • Lichun Chen
  • Wei Guo
  • Xiuyu Guo
  • Bing Hao
  • Yesen Li
Original Article


Tumor necrosis factor receptor 1 (TNFR1) is overexpressed in several varieties of carcinoma, including breast cancer. WH701 (Ala-Thr-Ala-Gln-Ser-Ala-Tyr-Gly), which was identified by phage display, can specifically bind to TNFR1. In this study, we labeled WH701 with 18F and investigated its tumor diagnostic value. WH701 was synthesized by standard Fmoc-solid phase synthetic protocols and conjugated by NOTA–NHS. NOTA–WH701 was radiolabeled with 18F using NOTA–AlF chelation reaction. The tumor target properties were evaluated in vitro and in vivo using MCF-7 xenografts and inflammation models. [18F]AlF–NOTA–WH701 was labeled in 25 min with a decay-corrected yield of 38.1 ± 4.8% (n = 5) and a specific activity of 10.4–13.0 GBq/μmol. WH701 had relatively high affinity for MCF-7 cells in vitro and [18F]AlF–NOTA–WH701 displayed relatively high tumor uptake in vivo. The tumor to muscle ratio was 4.25 ± 0.56 at 30 min post-injection (p.i.); further, there was a significant difference between the tumor/muscle and inflammation/muscle (3.22 ± 0.56) ratio, which could differentiate the tumor and inflammation. The tumor uptake of [18F]AlF–NOTA–WH701 could be inhibited by 71.1% by unlabeled WH701 at 30 min p.i. We have developed a promising PET tracer [18F]AlF–NOTA–WH701 for the noninvasive detection of breast cancer in vivo.


WH701 PET imaging TNFR1 Breast cancer 18F 


Compliance with ethical standards


This study was funded by the National Natural Science Foundation of China (81471684) and the Natural Science Foundation of Fujian Province of China (Nos. 2015J01543, 2016J01642).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were in accordance with the ethical standards of the Xiamen University Institutional Animal Care and Use Committee.

Supplementary material

726_2017_2526_MOESM1_ESM.docx (505 kb)
Supplementary material 1 (DOCX 504 kb)


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Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Medical College of Xiamen UniversityXiamen UniversityXiamenChina
  2. 2.Department of Nuclear Medicine and Minnan PET CenterXiamen Cancer Hospital, The First Affiliated Hospital of Xiamen UniversityXiamenChina
  3. 3.State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, Center for Molecular Imaging and Translational Medicine, School of Public HealthXiamen UniversityXiamenChina

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