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.