Immuno-PET/CT Imaging of Trop2 with [ 18 F]AlF-RESCA-T4 Differentiates Lung Cancer from Inflammation

作者：Wei Huang, Min Cao, Yanfei Wu, You Zhang, Shuxian An, Xinbing Pan, Xinyuan Zhou, Hongda Shao, Yihui Guan, Gang Huang, Fabrizia Gelardi, Arturo Chiti, Fang Xie, Jianjun Liu, Weijun Wei · 发表于：Journal of Nuclear Medicine · 年份：2024 · DOI：10.2967/jnumed.124.268751 · 被引用次数：10 · 研究领域：Radiopharmaceutical Chemistry and Applications、Peptidase Inhibition and Analysis、RNA modifications and cancer

Immuno-PET/CT imaging, a branch of molecular imaging, can noninvasively and specifically visualize biomarker expression across the body. Trophoblast cell surface antigen 2 (Trop2) is a pan-cancer biomarker and plays a crucial role in tumorigenesis through multiple signaling pathways. The study aims to develop and translate novel Trop2 single-domain antibody (sdAb) tracers for clinical use. Methods: Two sdAbs (i.e., His-tagged T4 and His-tag−free RT4) are recombinantly expressed in Chinese hamster ovary cells. The purities and binding kinetics are determined by sodium dodecyl sulfate polyacrylamide gel electrophoresis, high-performance liquid chromatography, and surface plasmon resonance assays. The AlF restrained complexing agent (RESCA) method is applied to develop 18 F-labeled sdAb tracers ([ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4), followed by thorough preclinical imaging and blocking studies on tumor-bearing mice and a pilot clinical trial evaluating the clinical imaging safety and feasibility of [ 18 F]AlF-RESCA-T4 immuno-PET/CT. Results: [ 18 F]AlF-RESCA-T4 and [ 18 F]AlF-RESCA-RT4 possess high radiochemical purities. Preclinical imaging in the T3M-4 tumor model revealed prominent uptake (percentage injected dose/g) of [ 18 F]AlF-RESCA-T4 (11.13 ± 1.53, n = 4) and [ 18 F]AlF-RESCA-RT4 (8.83 ± 1.22, n = 4), which were significantly reduced by coinjection of unlabeled T4 and RT4 in blocking studies. The His-tag removal strategy further optimized the probe’s i...