Synthesis and Preclinical Evaluation of [F]AlF-NOTA-A2P-GPC3P for Imaging of GPC3.

To develop an effective GPC3-targeted PET probe for tumor imaging, [F]AlF-NOTA-A2P-GPC3P was synthesized by introducing the hydrophilic linker A2P into the L5 peptide scaffold. The probe was efficiently radiolabeled using the [F]AlF method, exhibiting high hydrophilicity (Log  = -3.11 ± 0.31) and excellent in vitro and in vivo stability. Cellular uptake assays verified that the probe was significantly more highly taken up by GPC3-positive cell lines than by GPC3-low cell lines, confirming its specific binding to GPC3-positive cells. Micro-PET/CT and biodistribution studies in GPC3-positive tumor models (ASPC1, A549-GPC3) demonstrated specific uptake, significantly improved tumor-to-background ratios (especially tumor-to-lung and tumor-to-heart ratios), and reduced hepatic accumulation compared with the reported probe. Blocking studies in GPC3-positive tumors (ASPC1) confirmed its specificity. Thus, [F]AlF-NOTA-A2P-GPC3P is a promising PET imaging agent for GPC3-positive tumor detection.