Evidence map›Paper›PMID 41840180›Full record

ArticleEJNMMI radiopharmacy and chemistry2026

Increased affinity by dimerization of radiolabeled Affibody molecule ATH001 targeting PDGFRβ.

Ayman Abouzayed, Hugo Olsson, Natalia Papadopoulos, Bogdan Mitran, Hemantha Mallapura, Tahmida Akter, Irina Velikyan, Olle Korsgren, Carl-Henrik Heldin, John Löfblom and 2 more

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Article in EJNMMI radiopharmacy and chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Ayman AbouzayedScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 751 83, Uppsala, Sweden.
Hugo OlssonDivision of Protein Engineering, Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden.
Natalia PapadopoulosSciLifeLab, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Bogdan MitranScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 751 83, Uppsala, Sweden.
Hemantha MallapuraScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 751 83, Uppsala, Sweden.
Tahmida AkterScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 751 83, Uppsala, Sweden.
Irina VelikyanScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 751 83, Uppsala, Sweden.
Olle KorsgrenDepartment of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Carl-Henrik HeldinSciLifeLab, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
John LöfblomDivision of Protein Engineering, Department of Protein Science, KTH Royal Institute of Technology, Stockholm, Sweden.
Michael WagnerAntaros Tracer AB, Uppsala, Sweden.
Olof ErikssonScience for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, 751 83, Uppsala, Sweden. olof.eriksson@ilk.uu.se.ORCID http://orcid.org/0000-0002-2515-8790

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPlatelet-derived growth factor receptor-β (PDGFRβ) is a canonical marker of pericytes and stromal cells in most tissues. It is present on cancer associated fibroblasts (CAFs) in the tumor microenvironment and has thus been proposed as a potential therapeutic target both for anti-cancer drugs as well as for radioligand therapy (RLT). ATH001 is a novel Affibody molecule-based radiopharmaceutical in clinical development for targeting of PDGFRβ. We hypothesize that dimerization of ATH001 could improve affinity to PDGFRβ, leading to better characteristics for in vivo targeting. The dimeric construct, named ATH022, was generated by conjugation of two chemically synthesized ATH001 binders to a tri-functional linker comprising a DOTA chelator. Here, we present a comprehensive in vitro and in vivo evaluation of Gallium-68 and Indium-111 labeled ATH022, in direct comparison with ATH001.

resultsDOTA-ATH022 acted as a PDGFRβ antagonist and competed dose-dependently with the endogenous ligand PDGF-BB. Affinity of the dimer was improved approximately tenfold compared to DOTA-ATH001, mainly due to strongly decreased off-rate. Radiolabeled DOTA-ATH022 demonstrated higher specific binding and longer retention to U87 cells in vitro. Radiolabeled DOTA-ATH022 also exhibited elevated binding in PDGFRβ-positive tissues spleen and U87 tumors, that could be blocked by ATH001 in excess. Binding of DOTA-ATH022 in PDGFRβ avid and well-perfused spleen was 3 times higher than for DOTA-ATH001, but tumor binding was lower. In vivo retention in spleen was 5 times longer for Indium-111 labeled ATH022, in agreement with its in vitro binding characteristics.

conclusionsDOTA-ATH022 is a novel dimerized version of ATH001, with significantly improved affinity towards PDGFRβ. Retention of radiolabeled DOTA-ATH022 in PDGFRβ-avid tissues and tumors was increased, however uptake in solid tumor tissue was not improved.

Indexed as

AffibodyDimerPETPlatelet-derived growth factor receptorRadioligand therapy

Identifiers

PMID41840180
PMCPMC13066081

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.