Pre-clinical study of a TNFR1-targeted 18F probe for PET imaging of breast cancer
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.
KeywordsWH701 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.
All procedures performed in studies involving animals were in accordance with the ethical standards of the Xiamen University Institutional Animal Care and Use Committee.
- Hao R, Lin Z, Shibin F, Bo T, Qianwei L (2013) Preparation of 99mTc-TP1093 and its bio-distribution and kinetic characteristics in healthy animals. J Third Mil Med Univ 35:769–773Google Scholar
- Jingsong X, Yan X, Hua W (2005) Selection of peptide ligands for TNF receptor imaging Chinese. J Nucl Med 25:43–45Google Scholar
- Madeleine MM, Johnson LG, Malkki M, Resler AJ, Petersdorf EW, McKnight B, Malone KE (2011) Genetic variation in proinflammatory cytokines IL6, IL6R, TNF-region, and TNFRSF1A and risk of breast cancer. Breast Cancer Res Treat 129:887–899. https://doi.org/10.1007/s10549-011-1520-4 CrossRefPubMedPubMedCentralGoogle Scholar
- Mammatas LH, Verheul HM, Hendrikse NH, Yaqub M, Lammertsma AA, Menke-van der Houven van Oordt CW (2015) Molecular imaging of targeted therapies with positron emission tomography: the visualization of personalized cancer care. Cell Oncol (Dordr) 38:49–64. https://doi.org/10.1007/s13402-014-0194-4 CrossRefGoogle Scholar
- Pellegrino D, Bonab AA, Dragotakes SC, Pitman JT, Mariani G, Carter EA (2005) Inflammation and infection: imaging properties of 18F-FDG-labeled white blood cells versus 18F-FDG. J Nucl Med Off Publ Soc Nucl Med 46:1522–1530Google Scholar