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177Lu-labeled DOTA-EB-RGD as a Candidate for Thyroid Cancer Therapy

ABSTRACT: Integrin αVβ3, a transmembrane receptor involved in tumor growth and metastasis, specifically recognizes and binds proteins with the arginylglycylaspartyl (RGD) peptide sequence. Using mRNA and/or protein expression data from 496 thyroid cancer (TC) samples in The Cancer Genome Atlas (TCGA), 14 TC cell lines, and 70 TC and 10 normal thyroid tissues, we found that papillary TC exhibits the highest αVβ3 integrin expression. We then evaluated the therapeutic efficacy of a novel radiolabeled RGD analog, 177Lu-DOTA-EB-cRGDfK, in TC. Genetic knockout and overexpression of αVβ3 in TC cell lines confirmed the target specificity of 177Lu-DOTA-EB-cRGDfK. In mouse xenograft models established from human TC cell lines with high αVβ3 expression, 177Lu-DOTA-EB-cRGDfK demonstrated superior antitumor efficacy compared with standard-of-care lenvatinib and placebo. However, no synergistic benefit was observed with combination therapy. Biodistribution studies identified the kidneys as the dose-limiting organ. RNA-seq analysis of resected tumors demonstrated that 177Lu-DOTA-EB-cRGDfK induced type I interferon response, characterized by upregulation of IFI6, IFIT1-2, MX1, compared with both lenvatinib-treated tumors and placebo. These findings identify αVβ3 integrin as a promising therapeutic target in a subset of TCs and demonstrate that 177Lu-DOTA-EB-cRGDfK exhibits superior efficacy to lenvatinib, supporting its potential clinical translation for progressive TC refractory to standard therapies.

ORGANISM(S): Mus musculus

PROVIDER: GSE343650 | GEO | 2026/08/17

REPOSITORIES: GEO

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177Lu-labeled DOTA-EB-RGD as a Candidate for Thyroid Cancer Therapy

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