Preclinical evaluation of [(13x)La]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein

对[(13x)La]La-FAP-2286作为一种新型治疗诊断剂在表达成纤维细胞活化蛋白的肿瘤中的临床前评估

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Abstract

In this study, a novel theranostic radiopharmaceutical, [(13x)La]La-FAP-2286, for targeting Fibroblast Activation Protein (FAP)-positive tumors. The theranostic pair of (132)La (half-life: 4.59 h, 42.1% β⁺) and (135)La (half-life: 18.91 h, 100% EC) was produced via proton bombardment of natural barium in a 30 MeV cyclotron, achieving high radionuclidic purity (99.9%) and radiochemical purity (RCP > 99%). Stability tests revealed the RCP greater than 91% over 24 h in human serum and PBS buffer. Cellular studies confirmed high binding affinity (K(D) = 0.51 ± 0.12 nM) and effective internalization of [(13x)La]La-FAP-2286 in FAP + tumor cells. Distribution coefficient (log D) measurements demonstrated high hydrophilicity of the complex with a value of - 3.21 ± 0.14. Imaging and biodistribution studies in tumor-bearing mice further confirmed tumor targeting, with significant uptake observed up to 48 h post-injection. These results suggest [(13x)La]La-FAP-2286 can be considered a candidate for theranostic applications, offering both practical PET imaging and targeted Auger-electron therapy for cancer treatment.

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