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.