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Whole-body molecular imaging with [18F]FDG and [18F]FES PET/CT helps, yet often cannot capture other relevant molecular pathways. This review discusses validated and emerging standard-of-care and novel molecular imaging approaches and evaluates potential PARP inhibitor-based radiopharmaceuticals as non-invasive biomarkers of PARP expression or upregulation, linking imaging findings to patient 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Cancer for Improved Clinical Management: Current Practice and Future Perspectives  \nHonest Ndlovu 1,2, Ismaheel O. Lawal 2,3, Kgomotso M. G. Mokoala 1,2 and Mike M. Sathekge 1,2, *  \nCitation: Ndlovu, H.; Lawal, I.O.; Mokoala, K.M.G.; Sathekge, M.M. Imaging Molecular Targets and Metabolic Pathways in Breast Cancer for Improved Clinical Management: Current Practice and Future Perspectives. Int. J. Mol. Sci. 2024, 25, 1575. [https://doi.org/10.3390/](https://doi.org/10.3390/)[ ](https://doi.org/10.3390/)ijms25031575  \nAcademic Editor: Hidetaka Kawabata  \nReceived: 9 December 2023  \nRevised: 23 January 2024  \nAccepted: 24 January 2024  \nPublished: 26 January 2024  \nCopyright: © 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ([https://](https://)[ ](https://)[creativecommons.org/licenses/by/](creativecommons.org/licenses/by/)[ ](creativecommons.org/licenses/by/)[4.0/](4.0/)) .  \n1 Nuclear Medicine Research Infrastructure (NuMeRI), Steve Biko Academic Hospital, Pretoria 0001, South Africa; [ndlovuhonest@gmail.com](ndlovuhonest@gmail.com) (H.N.); [kgomotso.mokoala@up.ac.za](kgomotso.mokoala@up.ac.za) (K.M.G.M.)  \n2 Department of Nuclear Medicine, University of Pretoria & Steve Biko Academic Hospital, Private Bag X169, Pretoria 0001, South Africa; [ismaheel.opeyemi.lawal@emory.edu](ismaheel.opeyemi.lawal@emory.edu)  \n3 Department of Radiology and Imaging Sciences, Emory University, Atlanta, GA 30322, USA  \n* [Correspondence: mike.sathekge@up.ac.za](Correspondence: mike.sathekge@up.ac.za); Tel.: +27-12-354-1794  \nAbstract: Breast cancer is the most frequently diagnosed cancer and leading cause of cancer-related deaths worldwide. Timely decision-making that enables implementation of the most appropriate therapy or therapies is essential for achieving the best clinical outcomes in breast cancer. While clinicopathologic characteristics and immunohistochemistry have traditionally been used in decisionmaking, these clinical and laboratory parameters may be difficult to ascertain or be equivocal due to tumor heterogeneity. Tumor heterogeneity is described as a phenomenon characterized by spatial or temporal phenotypic variations in tumor characteristics. Spatial variations occur within tumor lesions or between lesions at a single time point while temporal variations are seen as tumor lesions evolve with time. Due to limitations associated with immunohistochemistry (which requires invasive biopsies), whole-body molecular imaging tools such as standard-of-care [18F]FDG and [18F]FES PET/CT are indispensable in addressing this conundrum. Despite their proven utility, these standardof-care imaging methods are often unable to image a myriad of other molecular pathways associated with breast cancer. This has stimulated interest in the development of novel radiopharmaceuticals targeting other molecular pathways and processes. In this review, we discuss validated and potential roles of these standard-of-care and novel molecular approaches. These approaches’ relationships with patient clinicopathologic and immunohistochemical characteristics as well as their influence on patient management will be discussed in greater detail. This paper will also introduce and discuss the potential utility of novel PARP inhibitor-based radiopharmaceuticals as non-invasive biomarkers of PARP expression/upregulation.  \nKeywords: breast cancer; tumor heterogeneity; immunohistochemistry; receptor expression; standard imaging; tumor microenvironment; PARP imaging  \n1. Introduction  \nWorldwide, breast cancer has a significant contribution to cancer-related morbidity and mortality. It accounts for 30% of female-related cancers and has a mortality-toincidence ratio of 15%[1,2] . Patient outcomes in breast cancer heavily depend on prompt decision-making that enables th","cbCaic6nWWGNwamJ","https://ap.wps.com/l/cbCaic6nWWGNwamJ","pdf",2978510,24,"English","# Abstract\n# Keywords\n# 1. Introduction","[{\"question\":\"Why is timely decision-making important in breast cancer management?\",\"answer\":\"Timely decisions enable implementation of the most appropriate therapy or therapies, supporting better clinical outcomes.\"},{\"question\":\"What role does tumor heterogeneity play in breast cancer diagnosis and imaging needs?\",\"answer\":\"Tumor heterogeneity involves spatial or temporal phenotypic variations, which can make clinicopathologic characteristics and immunohistochemistry difficult or equivocal.\"},{\"question\":\"How do standard-of-care molecular imaging tools help, and what is their limitation?\",\"answer\":\"Whole-body molecular imaging tools like [18F]FDG and [18F]FES PET/CT address heterogeneity, but they often cannot image many other molecular pathways relevant to breast cancer.\"}]","Imaging Molecular Targets and Metabolic Pathways in Breast Cancer for Improved Clinical Management - Current Practice and Future Perspectives | PDF",1790039418]