ArticleEJNMMI radiopharmacy and chemistry2025
PDGFRß targeted positron emission tomography as a non-invasive biomarker for activated hepatic stellate cells: lasts steps before clinical translation.
Article in EJNMMI radiopharmacy and chemistry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- Imaging of MASLD: clinical standards and novel methods.Diabetologia · 2026Review
- Biodistribution and radiation dosimetry of the PDGFRβ targeting PET tracer [European journal of nuclear medicine and molecular imaging · 2026Article
- Highlight selection of radiochemistry and radiopharmacy developments by editorial board.EJNMMI radiopharmacy and chemistry · 2026Article
- Increased affinity by dimerization of radiolabeled Affibody molecule ATH001 targeting PDGFRβ.EJNMMI radiopharmacy and chemistry · 2026Article
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16 authors.
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Abstract
backgroundActivated hepatic stellate cells (aHSCs) are the key cell population in the injured liver driving fibrogenesis. aHSCs express platelet-derived growth factor receptor beta (PDGFRß), which is absent from quiescent HSCs. PDGFRß is therefore an attractive target of PET tracers for imaging of fibrogenesis. Here, we present the pharmacological characterization of [68Ga]Ga-DOTA-Cys-ATH001 in preparation for clinical translation and further confirm PDGFRß as a biomarker of activated HSCs in liver disease by single cell sequencing.
methodsThe expression of PDGFRß in subpopulations of HSCs was evaluated in scRNAseq datasets from both a mouse and human liver samples. DOTA-Cys-ATH001 was evaluated for affinity and mechanism of binding to PDGFRß. [68Ga]Ga-DOTA-Cys-ATH001 was evaluated for binding in vitro in mouse and human liver biopsies. The in vivo stability, biodistribution, pharmacokinetics, dosimetry and microdosing toxicology were evaluated in rats and pigs.
resultsPDGFRß expression was specifically upregulated in activated HSCs. [68Ga]Ga-DOTA-Cys-ATH001 could differentiate fibrotic liver from healthy liver. The binding co-localized with tissue areas positive for collagen deposition and PDGFRß immunostaining. Based on the microdosing toxicology study the no observed adverse effect level was at least 1000 µg/kg, suggesting that the intended clinical PET scan dose is safe for use. Dosimetry calculations of [68Ga]Ga-DOTA-Cys-ATH001 predicted an effective dose in human amenable to repeated examinations.
conclusionsThe data presented here suggests that PDGFRβ PET imaging with [68Ga]Ga-DOTA-Cys-ATH001 has potential for non-invasive detection of activated HSCs. Clinical translation of [68Ga]Ga-DOTA-Cys-ATH001 is ongoing.
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