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REVIEW ARTICLE

Exploring tumor heterogeneity: The role of PET/CT with various radiopharmaceuticals in diagnosis and treatment guidance

Anjali Jain1* ,  Subhash Kheruka1 ,  Sharjeel Usmani1 ,  Khulood Al Riyami1 ,  Asiya Al Busaidi1 ,  Sumit Bichpuria1 ,  Rashid Al Sukaiti1
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1 Department of Radiology and Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and Research Center, University Medical City, Muscat, Oman
ARNM, 025040005 https://doi.org/10.36922/ARNM025040005
Submitted: 21 January 2025 | Revised: 19 February 2025 | Accepted: 5 March 2025 | Published: 20 March 2025
(This article belongs to the Special Issue Recent Developments in Radiopharmaceuticals)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Cancer development is a multi-step process that undergoes multiple alterations over time. The tumor microenvironment (TME) contains tumor cells and stroma, including blood cells, fibroblasts, and immune cells, which undergo spatial and temporal changes. These changes contribute to tumor heterogeneity, leading to treatment failure and poor prognosis. As we move toward personalized medicine with the approval of targeted and other therapies, identifying tumor heterogeneity is becoming crucial to management. Positron emission tomography/computed tomography (PET/CT) with various radiopharmaceuticals plays an important role in diagnosing and highlighting heterogeneity non-invasively, guiding treatment decisions, and assessing treatment response. Variability in tracer distribution of 18F-fluorodeoxyglucose (FDG) and various radiopharmaceuticals when coupled together can target various tumor characteristics and, therefore, play an important role in diagnosing heterogeneity. Some of the commonly paired radiopharmaceuticals include 18F-FDG with 68Gallium DOTA (1,4,7,10-tetraazacyclododecane-tetraacetic acid) peptide for neuroendocrine tumors, 18F-FDG with 68Ga-prostate specific membrane antigen for prostate cancers, 18F-metafluorobenzylguanidine with 18F-FDG and 68Ga-DOTA peptide for neural crest tumors, and 18F-fluoroestradiol with 18F-FDG for breast cancers. Many other tracers, including 68Ga-fibroblast activation protein inhibitor and labeled integrins, attach to various components on tumor cells and TME and have displayed significantly positive effects in certain tumors. However, their potential role as a biomarker to evaluate tumor heterogeneity and its clinical relevance remains largely uninvestigated.

Keywords
Cancer
Heterogeneity
18F- FDG
PET/CT
Funding
None.
Conflict of interest
The authors declare that they have no competing interests.
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