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PCa mortality and morbidity are primarily related to its most advanced form, metastatic castration\u2010resistant PCa (mCRPC), for which there is presently no cure. Therefore, novel therapeutic approaches to increase mCRPC survival are critically needed. Due to PCa tumor heterogeneity and a complex tumor microenvironment, the efficacy of single\u2010target radiopharmaceuticals, such as the Food and Drug Administration\u2010approved [<jats:sup>177<\/jats:sup>Lu]Lu\u2010PSMA\u2010617, is currently under reassessment. The design and development of PCa dual\u2010target radiopharmaceuticals have garnered considerable attention, due to their benefits over single\u2010target counterparts, namely increased therapeutic specificity and efficacy, as well as the ability to overcome the challenge of inconsistent tumor visualization caused by variable receptor expression across diverse lesions, thereby enabling more comprehensive imaging. Several PCa biomarkers are currently being investigated as potential targets for dual\u2010target radiopharmaceuticals, including prostate\u2010specific membrane antigen, gastrin\u2010releasing peptide receptor, integrin \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> receptor, fibroblast activation protein, sigma\u20101 receptor, as well as albumin, the radiosensitive cell nucleus, and mitochondria. This review explores recent advancements in heterobivalent metal\u2010based radiopharmaceuticals for dual targeting in PCa, highlighting their significance in theranostic and personalized medicine.<\/jats:p>","DOI":"10.1002\/cmdc.202500128","type":"journal-article","created":{"date-parts":[[2025,3,22]],"date-time":"2025-03-22T01:21:04Z","timestamp":1742606464000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Two Targets, One Mission: Heterobivalent Metal\u2010Based Radiopharmaceuticals for Prostate Cancer Imaging and Therapy"],"prefix":"10.1002","volume":"20","author":[{"given":"Margarida C.","family":"Sobral","sequence":"first","affiliation":[{"name":"Institute of Interdisciplinary Research University of Coimbra  3030\u2010789 Coimbra Portugal"},{"name":"CNC\u2010UC Center for Neuroscience and Cell Biology University of Coimbra  3060\u2010197 Cantanhede Portugal"},{"name":"CIBB Center for Innovative Biomedicine and Biotechnology University of Coimbra  3000\u2010548 Coimbra Portugal"},{"name":"Molecular Physical Chemistry R&amp;D Unit Department of Life Sciences University of Coimbra  3000\u2010456 Coimbra Portugal"}]},{"given":"Sandra I.","family":"Mota","sequence":"additional","affiliation":[{"name":"CNC\u2010UC Center for Neuroscience and Cell Biology University of Coimbra  3060\u2010197 Cantanhede Portugal"},{"name":"CIBB Center for Innovative Biomedicine and Biotechnology University of Coimbra  3000\u2010548 Coimbra Portugal"}]},{"given":"Paulo J.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"CNC\u2010UC Center for Neuroscience and Cell Biology University of Coimbra  3060\u2010197 Cantanhede Portugal"},{"name":"CIBB Center for Innovative Biomedicine and Biotechnology University of Coimbra  3000\u2010548 Coimbra Portugal"}]},{"given":"Ana M.","family":"Urbano","sequence":"additional","affiliation":[{"name":"Molecular Physical Chemistry R&amp;D Unit Department of Life Sciences University of Coimbra  3000\u2010456 Coimbra Portugal"},{"name":"Center of Investigation in Environment Genetics and Oncobiology (CIMAGO) University of Coimbra  3001\u2010301 Coimbra Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9164-0913","authenticated-orcid":false,"given":"Ant\u00f3nio","family":"Paulo","sequence":"additional","affiliation":[{"name":"C2TN \u2010Center for Nuclear Sciences and Technologies Instituto Superior T\u00e9cnico University of Lisboa  2695\u2010066 Lisboa Portugal"},{"name":"Department of Engineering and Nuclear Sciences Instituto Superior T\u00e9cnico University of Lisboa  2695\u2010066 Lisboa Portugal"}]}],"member":"311","published-online":{"date-parts":[[2025,4,7]]},"reference":[{"key":"e_1_2_8_2_1","volume":"1","author":"Adams J.","year":"1853","journal-title":"Lancet"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834"},{"key":"e_1_2_8_4_1","unstructured":"International Agency for Research on Cancer Global Cancer Observatory: Cancer Today n.d. 2025https:\/\/gco.iarc.fr\/today\/en(accessed: July 2024)."},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29894"},{"volume-title":"Prostate Cancer","year":"2024","author":"Leslie S. 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