Imaging of ROR1 expression in tumors using radiolabeled affibody molecules.

Authors

Cornelia Westerberg, Tianqi Xu, Maria Marth, Moeen Ud-Din, Russol Abushaia, Tilde Hagelin, Stefan Ståhl, Anna Orlova, Vladimir Tolmachev, John Löfblom, Anzhelika Vorobyeva

Published in

European journal of nuclear medicine and molecular imaging. Aug 01, 2026. Epub Aug 01, 2026.

Abstract

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an attractive molecular target for anti-tumor therapies undergoing late-stage clinical development. Quantitative imaging of ROR1 expression could enable identification of patients likely to respond to such treatments. This study aimed to assess the feasibility of specific in vivo imaging of ROR1 using radiolabeled affibody molecules.
The affibody molecule ZROR1:A10, with high affinity for human (4 nM) and murine (2 nM) ROR1, was labeled with indium-111 using a DOTA chelator. In vitro binding specificity, affinity, and cellular processing were evaluated using a panel of ROR1-expressing cell lines. The affibody [¹¹¹In]In-DOTA-Zcov19s, which does not bind ROR1, served as a nonspecific control. The biodistribution of [¹¹¹In]In-DOTA-ZROR1:A10 and [¹¹¹In]In-DOTA-Zcov19s was measured in immunodeficient mice bearing ROR1-positive tumors, with ROR1-negative Ramos xenografts used as an additional specificity control.
[¹¹¹In]In-DOTA-ZROR1:A10 bound specifically to ROR1-expressing cells, with significantly higher uptake than [¹¹¹In]In-DOTA-Zcov19s. The apparent equilibrium dissociation constant for ROR1 binding in vitro was 1-4 nM. Tumor uptake of [¹¹¹In]In-DOTA-ZROR1:A10 in MDA-MB-468 xenografts was saturable and significantly (p < 0.05) higher than in Ramos tumors, as well as higher than uptake of the control affibody. At 4 h post‑injection of 1 µg (50 µg/kg), tumor‑to‑blood, tumor‑to‑bone, and tumor‑to‑muscle ratios were 14 ± 6, 19 ± 6, and 11 ± 1, respectively. Micro-SPECT/CT imaging clearly visualized ROR1‑positive tumors and discriminated them from ROR1‑negative xenografts.
The preclinical evaluation shows that visualization of ROR1-expressing tumors using a radiolabeled affibody molecule is feasible.

PMID:
42538452
Bibliographic data and abstract were imported from PubMed on 01 Aug 2026.

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