Preclinical Evaluation of 68 Ga/ 177 Lu-Labeled FAP-Targeted Peptide for Tumor Radiopharmaceutical Imaging and Therapy

作者：Rang Wang, Mingxing Huang, Weichen Wang, Mufeng Li, Yingwei Wang, Rong Tian · 发表于：Journal of Nuclear Medicine · 年份：2025 · DOI：10.2967/jnumed.124.268689 · 被引用次数：23 · 研究领域：Peptidase Inhibition and Analysis、Neuropeptides and Animal Physiology、Chemical Synthesis and Analysis

Fibroblast activation protein (FAP) has been considered a promising target for tumor imaging and therapy. This study designed a novel peptide, FAP-HXN, specifically targeting FAP and exhibiting significant potential as a radionuclide-labeled theranostic agent. Preclinical studies were conducted to evaluate the potency, selectivity, and efficacy of FAP-HXN. Methods: FAP-HXN was synthesized and characterized for selectivity and specificity toward FAP. Cellular uptake of the radiolabeled FAP-HXN in human embryonic kidney (HEK)-293-FAP cells with high expressions of FAP was evaluated. The diagnostic and therapeutic potential of 68 Ga- and 177 Lu-labeled radioligands was evaluated in HEK-293-FAP tumor-bearing mice compared with the FAP-targeting peptide FAP-2286. Results: FAP-HXN demonstrated high binding ability to human and mouse sources of FAP. Moreover, the in vivo studies confirmed the high affinity and specificity of radiolabeled FAP-HXN. Small-animal PET imaging demonstrated that [ 68 Ga]Ga-FAP-HXN had continuous tumor uptake in FAP-positive tumors after administration compared with [ 68 Ga]Ga-FAP-2286. In the therapeutic experiments, [ 177 Lu]Lu-FAP-HXN showed significant antitumor activity in HEK-293-FAP xenografts at well-tolerated doses, which also exhibited longer tumor retention and better tumor growth inhibition compared with [ 177 Lu]Lu-FAP-2286. Conclusion: The preclinical studies revealed that radiolabeled FAP-HXN had high tumor uptake, prolonged rete...