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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\n                      <jats:italic>in vivo<\/jats:italic>\n                      imaging of ROR1 using radiolabeled affibody molecules.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The affibody molecule ZROR1:A10, with high affinity for human (4\u00a0nM) and murine (2\u00a0nM) ROR1, was labeled with indium-111 using a DOTA chelator.\n                      <jats:italic>In vitro<\/jats:italic>\n                      binding specificity, affinity, and cellular processing were evaluated using a panel of ROR1-expressing cell lines. The affibody [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-DOTA-Zcov19s, which does not bind ROR1, served as a nonspecific control. The biodistribution of [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-DOTA-ZROR1:A10 and [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-DOTA-Zcov19s was measured in immunodeficient mice bearing ROR1-positive tumors, with ROR1-negative Ramos xenografts used as an additional specificity control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-DOTA-ZROR1:A10 bound specifically to ROR1-expressing cells, with significantly higher uptake than [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-DOTA-Zcov19s. The apparent equilibrium dissociation constant for ROR1 binding\n                      <jats:italic>in vitro<\/jats:italic>\n                      was 1\u20134\u00a0nM. Tumor uptake of [\n                      <jats:sup>111<\/jats:sup>\n                      In]In-DOTA-ZROR1:A10 in MDA-MB-468 xenografts was saturable and significantly (p\u2009&lt;\u20090.05) higher than in Ramos tumors, as well as higher than uptake of the control affibody. At 4\u00a0h post\u2011injection of 1\u00a0\u00b5g (50\u00a0\u00b5g\/kg), tumor\u2011to\u2011blood, tumor\u2011to\u2011bone, and tumor\u2011to\u2011muscle ratios were 14\u2009\u00b1\u20096, 19\u2009\u00b1\u20096, and 11\u2009\u00b1\u20091, respectively. Micro-SPECT\/CT imaging clearly visualized ROR1\u2011positive tumors and discriminated them from ROR1\u2011negative xenografts.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The preclinical evaluation shows that visualization of ROR1-expressing tumors using a radiolabeled affibody molecule is feasible.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00259-026-08106-8","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T01:41:53Z","timestamp":1785548513000},"page":"8104-8115","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Imaging of ROR1 expression in tumors using radiolabeled affibody molecules"],"prefix":"10.1007","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0274-063X","authenticated-orcid":false,"given":"Cornelia","family":"Westerberg","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1826-4093","authenticated-orcid":false,"given":"Tianqi","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Marth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4542-1258","authenticated-orcid":false,"given":"Moeen","family":"Ud-Din","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russol","family":"Abushaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tilde","family":"Hagelin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9282-0174","authenticated-orcid":false,"given":"Stefan","family":"St\u00e5hl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6120-2683","authenticated-orcid":false,"given":"Anna","family":"Orlova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6122-1734","authenticated-orcid":false,"given":"Vladimir","family":"Tolmachev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9423-0541","authenticated-orcid":false,"given":"John","family":"L\u00f6fblom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4778-3909","authenticated-orcid":false,"given":"Anzhelika","family":"Vorobyeva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"8106_CR1","doi-asserted-by":"publisher","first-page":"496","DOI":"10.1007\/s13238-014-0059-7","volume":"5","author":"N Borcherding","year":"2014","unstructured":"Borcherding N, Kusner D, Liu GH, Zhang W. 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Vladimir Tolmachev and Anna Orlova are members of technical advisory boards for Affibody AB, Solna, Sweden, Anzhelika Vorobyeva is an advisor with Affibody AB, and received consultant honoraria. Anna Orlova, Vladimir Tolmachev, Stefan St\u00e5hl, John L\u00f6fblom and Anzhelika Vorobyeva are co-founders of the company Zytox Therapeutics AB, Stockholm, Sweden.","order":2,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}]}}