ArticleEJNMMI research2026
Head-to-head comparison of FAP-targeting single-domain antibody 4AH29 vs. peptide FAP-2286.
Article in EJNMMI research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Automated and manual synthesis of [EJNMMI radiopharmacy and chemistry · 2026Article
- Head-to-Head Comparison of Monomeric, Homodimeric, and Heterodimeric Fibroblast Activation Protein-Targeting Radioligands Based on Small Molecule Inhibitor and Cyclic Peptide.ACS pharmacology & translational science · 2026Article
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11 authors.
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Abstract
backgroundRadiolabeled FAP-targeting sdAb 4AH29 was developed previously, showing potent therapeutic efficacy. This head-to-head study compares sdAb 4AH29 and peptide FAP-2286, generally considered as most clinically advanced, for their in vitro and in vivo tumor retention, resulting dosimetry, and therapeutic efficacy in relevant rodent tumor models.
resultsIn vitro, [177Lu]Lu-DOTA-4AH29 showed sustained cell-associated activity until 48 h, whereas it dropped to baseline within the first hours for [177Lu]Lu-DOTA-FAP-2286. In vivo, in U87-MG, [177Lu]Lu-DOTA-FAP-2286 accumulated better at the tumor at early time points but from 24 h was significantly less retained than [177Lu]Lu-DOTA-4AH29, leading to a threefold higher absorbed dose to the tumor for [177Lu]Lu-DOTA-4AH29. Compared to U87-MG, absolute tumor uptake for both tracers in HT-29 was decreased, in line with lower FAP expression of this model. Of note, significant improved tumor retention was observed for [177Lu]Lu-DOTA-4AH29 over time, resulting in a twofold higher tumor absorbed dose. The transfected HEK-hFAP model showed an enhanced tumor uptake with [177Lu]Lu-DOTA-FAP-2286 at all assessed time points, displaying a 4.8 more elevated absorbed dose to tumor than [177Lu]Lu-DOTA-4AH29. Treatment with [177Lu]Lu-DOTA-4AH29 or [225Ac]Ac-DOTA-4AH29 significantly delayed U87-MG tumor development compared to [177Lu]Lu-DOTA-FAP-2286 43 days post inoculation. Survival was improved after administration of [225Ac]Ac-DOTA-4AH29 compared to [177Lu]Lu-DOTA-FAP-2286, whereas it was a trend with [177Lu]Lu-DOTA-4AH29. In HT-29, no significant differences in tumor control were observed at day 29 before first animal reached humane endpoint. Nevertheless, enhanced survival was achieved with a single shot of [225Ac]Ac-DOTA-4AH29 at 120 kBq.
conclusionsThese preclinical results underline the potential benefit of radiolabeled 4AH29 over FAP-2286 due to its enhanced tumor retention and more pronounced anti-tumor effects warranting clinical investigation.
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