Tao Yang, Jiahui Sun, Guolong Huang, Hong Wang, Zhanwen He, Siying Lin, Yanjie Wang, Rongqiang Zhuang, Xianzhong Zhang, Hongwu Liu, Zhide Guo
Abstract Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is highly upregulated in multiple cancers and serves as a promising biomarker for patient staging and therapy guidance. We designed five ROR1-targeted radiotracers, including linear and cyclic peptides derived from PR7, and evaluated their specificity and affinity in vitro and in vivo. All probes showed a rapid tumor uptake within 30 min in MC38 models. Saturation binding assays and blocking studies confirmed the ROR1 specificity. Positron emission tomography imaging with [68Ga]Ga-DP1 and [18F]AlF-NP1 demonstrated excellent tumor targeting and favorable target-to-nontarget ratios across multiple models, with renal clearance observed in biodistribution. Transcriptomic analysis indicated the potential involvement of ROR1 in the PI3K/AKT pathway. In general, these findings support [18F]AlF-NP1 and [68Ga]Ga-DP1 as promising noninvasive imaging agents for quantitative ROR1 visualization and personalized cancer therapy.