Design, Synthesis, and Biological Evaluation of [18F]AlF-Labeled Integrin αvβ6-Targeting Tracers for Pancreatic Cancer Imaging

Integrin αvβ6 is an attractive target for theranostic applications in pancreatic ductal adenocarcinoma (PDAC). Yet, there remains a lack of an ideal PET/CT tracer targeting αvβ6. In this study, we designed two novel PET/CT tracers [¹⁸F]AlF-Glc-αvβ6L and [¹⁸F]AlF-Asp2-αvβ6L with hydrophilic linkers. Both [¹⁸F]AlF-Glc-αvβ6L and [¹⁸F]AlF-Asp2-αvβ6L demonstrated favorable in vitro and in vivo properties, which are characterized by high hydrophilicity. In pancreatic tumor-bearing mice, micro-PET/CT imaging and biodistribution studies demonstrated that both [¹⁸F]AlF-Glc-αvβ6L and [¹⁸F]AlF-Asp2-αvβ6L had favorable pharmacokinetic properties, good specific targeting to αvβ6, and tumor-to-background contrast. Between them, [¹⁸F]AlF-Asp2-αvβ6L demonstrated superior in vivo stability and accelerated renal clearance than [¹⁸F]AlF-Glc-αvβ6L, with comparable tumor uptake and retention and significantly lower kidney uptake. The results indicate that [¹⁸F]AlF-Asp2-αvβ6L is a promising PET/CT tracer for PDAC imaging.