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

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 b...

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Main Authors: Ali Shirpour, Asghar Hadadi, Samaneh Zolghadri, Sara Vosoughi, Saeed Rajabifar
Format: Article
Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-025-91716-3
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author Ali Shirpour
Asghar Hadadi
Samaneh Zolghadri
Sara Vosoughi
Saeed Rajabifar
author_facet Ali Shirpour
Asghar Hadadi
Samaneh Zolghadri
Sara Vosoughi
Saeed Rajabifar
author_sort Ali Shirpour
collection DOAJ
description 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 (KD = 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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spelling doaj-art-6465d3129df6457486d8a87c49bcfecf2025-08-20T01:57:44ZengNature PortfolioScientific Reports2045-23222025-03-0115111310.1038/s41598-025-91716-3Preclinical evaluation of [13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation proteinAli Shirpour0Asghar Hadadi1Samaneh Zolghadri2Sara Vosoughi3Saeed Rajabifar4Department of Medical Radiation Engineering, Science and Research Branch, Islamic Azad UniversityDepartment of Medical Radiation Engineering, Science and Research Branch, Islamic Azad UniversityRadiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI)Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI)Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI)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 (KD = 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.https://doi.org/10.1038/s41598-025-91716-3
spellingShingle Ali Shirpour
Asghar Hadadi
Samaneh Zolghadri
Sara Vosoughi
Saeed Rajabifar
Preclinical evaluation of [13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein
Scientific Reports
title Preclinical evaluation of [13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein
title_full Preclinical evaluation of [13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein
title_fullStr Preclinical evaluation of [13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein
title_full_unstemmed Preclinical evaluation of [13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein
title_short Preclinical evaluation of [13xLa]La-FAP-2286 as a novel theranostic agent for tumors expressing fibroblast activation protein
title_sort preclinical evaluation of 13xla la fap 2286 as a novel theranostic agent for tumors expressing fibroblast activation protein
url https://doi.org/10.1038/s41598-025-91716-3
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