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Clinical use is challenging due to dose limiting side effects and severe anemia. Better understanding of the whole-body dynamics of CD47\/SIRP\u03b1 can be used to improve the developmental and therapeutic strategies targeting this axis. Herein, we developed anti-CD47 and anti-SIRP\u03b1 radiotracers with good yields and stability. CD47\/SIRP\u03b1 biodistribution showed consistent whole-body results in healthy and colorectal cancer (CT26) allograft mice, demonstrating significant uptake in normal organs liver and spleen in addition to tumor accumulation of these agents. Enhancing immunogenicity via low-dose radiotherapy had no impact on over-all biodistribution but caused small, significant changes for anti-SIRP\u03b1 tumor uptake. Antibody PEGylation of the anti-SIRP\u03b1 tracer was further able to modify the whole-body distribution and reduce splenic uptake. These findings suggest that SIRP\u03b1 targeted agents may benefit from co-therapies and drug delivery systems to optimize tumor uptake. Our work highlights the importance of in vivo molecular imaging in addition to in vitro and ex vivo assays when evaluating therapeutic designs.<\/jats:p>","DOI":"10.64898\/2026.01.28.702416","type":"posted-content","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T21:05:22Z","timestamp":1769720722000},"source":"Crossref","is-referenced-by-count":0,"title":["Positron Emission Tomography of CD47\/SIRP\u03b1 Axis and Image-Informed Therapeutic Design"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-0060-5504","authenticated-orcid":false,"given":"Esther D.","family":"Need","sequence":"first","affiliation":[{"name":"Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neetu","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayden","family":"Berndt","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alex","family":"Shelton","sequence":"additional","affiliation":[{"name":"School of Biological Science, University of Utah, Salt Lake City, UT 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samuel H.","family":"Cheshier","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, University of Utah, Salt Lake City, UT 84112"},{"name":"Huntsman Cancer Institute, University of Utah, Salt Lake City, UT 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shreya","family":"Goel","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112"},{"name":"Department of Biomedical Engineering, University of Utah, Salt Lake City, UT 84112"},{"name":"Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sixiang","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmaceutics, University of Utah, Salt Lake City, UT 84112"},{"name":"Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, UT 84112"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2026020510401820000_2026.01.28.702416v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"2026020510401820000_2026.01.28.702416v1.2","doi-asserted-by":"publisher","DOI":"10.3390\/biology12030472"},{"key":"2026020510401820000_2026.01.28.702416v1.3","doi-asserted-by":"publisher","DOI":"10.1136\/bmjph-2024-001995"},{"key":"2026020510401820000_2026.01.28.702416v1.4","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-021-00574-0"},{"key":"2026020510401820000_2026.01.28.702416v1.5","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-021-00155-y"},{"key":"2026020510401820000_2026.01.28.702416v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2021.04.021"},{"key":"2026020510401820000_2026.01.28.702416v1.7","doi-asserted-by":"publisher","DOI":"10.1158\/1538-7445.AM2018-1684"},{"key":"2026020510401820000_2026.01.28.702416v1.8","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2020.07.008"},{"key":"2026020510401820000_2026.01.28.702416v1.9","doi-asserted-by":"publisher","DOI":"10.1111\/j.1537-2995.2007.01348.x"},{"key":"2026020510401820000_2026.01.28.702416v1.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e20507"},{"key":"2026020510401820000_2026.01.28.702416v1.11","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109793"},{"key":"2026020510401820000_2026.01.28.702416v1.12","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M805729200"},{"key":"2026020510401820000_2026.01.28.702416v1.13","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.161.4.1853"},{"key":"2026020510401820000_2026.01.28.702416v1.14","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-10-386805"},{"key":"2026020510401820000_2026.01.28.702416v1.15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1121623109"},{"key":"2026020510401820000_2026.01.28.702416v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2009.05.045"},{"key":"2026020510401820000_2026.01.28.702416v1.17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052690"},{"key":"2026020510401820000_2026.01.28.702416v1.18","unstructured":"The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors | PNAS. 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