Preclinical evaluation of [^13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein.

IF 3.9 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Scientific Reports Pub Date : 2025-03-03 DOI:10.1038/s41598-025-91716-3

Ali Shirpour, Asghar Hadadi, Samaneh Zolghadri, Sara Vosoughi, Saeed Rajabifar

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Abstract

In this study, a novel theranostic radiopharmaceutical, [^13xLa]La-FAP-2286, for targeting Fibroblast Activation Protein (FAP)-positive tumors. The theranostic pair of ¹³²La (half-life: 4.59 h, 42.1% β⁺) and ¹³⁵La (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 [^13xLa]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 [^13xLa]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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[13xLa]La-FAP-2286作为表达成纤维细胞激活蛋白肿瘤的新型治疗剂的临床前评价

在这项研究中，一种新的治疗放射性药物，[13xLa]La-FAP-2286，用于靶向成纤维细胞活化蛋白（FAP）阳性肿瘤。132La（半衰期：4.59 h, 42.1%）和135La（半衰期：18.91 h, 100% EC）通过质子轰击天然钡在30 MeV回旋加速器中产生，获得了高放射性核素纯度（99.9%）和放射化学纯度（RCP > 99%）。稳定性试验表明，在人血清和PBS缓冲液中，24 h RCP大于91%。细胞研究证实了[13xLa]La-FAP-2286在FAP +肿瘤细胞中的高结合亲和力（KD = 0.51±0.12 nM）和有效内化。分布系数（log D）测量结果表明，该配合物具有较高的亲水性，值为- 3.21±0.14。荷瘤小鼠的成像和生物分布研究进一步证实了肿瘤靶向性，注射后48小时内观察到明显的摄取。这些结果表明，[13xLa]La-FAP-2286可以被认为是治疗应用的候选材料，为癌症治疗提供实用的PET成像和靶向俄歇电子治疗。

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来源期刊

Scientific Reports Natural Science Disciplines-

CiteScore

7.50

自引率

4.30%

发文量

19567

审稿时长

3.9 months

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