Development of [¹⁸F]AlF-RESCA-H006 as a Novel Molecular Probe for 5T4 Tumor Imaging and Exploration of Its Application in Pancreatic Adenocarcinoma

Pancreatic adenocarcinoma (PAAD) is an extremely lethal cancer, making early detection and precise staging essential for extending survival. Upregulation of 5T4 mRNA was detected in bioinformatics analysis using data from the Cancer Genome Atlas and Genotype-Tissue Expression. In the current work, we confirmed the overexpression of 5T4 protein in tumor samples of PAAD compared with the corresponding paraneoplastic tissue. To visualize 5T4 via positron emission tomography (PET) noninvasively, we successfully developed [¹⁸F]AlF-RESCA-H006 based on a single-domain antibody fragment. The radiotracer demonstrated high binding affinity toward 5T4 antigens <i>in vitro</i> and remained stable in the final formulation for up to 4 h storage at room temperature. In two preclinical mouse models of pancreatic cancer, [¹⁸F]AlF-RESCA-H006 clearly identified the tumor sites, showing a radioactivity accumulation of 2.43 ± 0.46% ID/g in Balb/C mice with BxPC-3 xenografts and 2.88 ± 1.02% ID/g in NCG mice with PANC-1 xenografts. Taken together, [¹⁸F]AlF-RESCA-H006 is a promising PET tracer for detecting 5T4 antigen alteration in PAAD. Further investigations are required to assess its defluorination level in higher species and its permeability through the dense extracellular matrix of pancreatic cancer.