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Advances in Radiotherapy &

Nuclear Medicine

REVIEW ARTICLE
Exploring tumor heterogeneity: The role of

PET/CT with various radiopharmaceuticals in
diagnosis and treatment guidance

Anjali Jain* , Subhash Kheruka , Sharjeel Usmani , Khulood Al Riyami ,
Asiya Al Busaidi , Sumit Bichpuria , and Rashid Al Sukaiti
Department of Radiology and Nuclear Medicine, Sultan Qaboos Comprehensive Cancer Care and
Research Center, University Medical City, Muscat, Oman
(This article belongs to the Special Issue: Recent Developments in Radiopharmaceuticals)

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
*Corresponding author:
Anjali Jain decisions, and assessing treatment response. Variability in tracer distribution of
(a.jain@cccrc.gov.om) 18 F-fluorodeoxyglucose (FDG) and various radiopharmaceuticals when coupled
Citation: Jain A, Kheruka S, together can target various tumor characteristics and, therefore, play an important role
Usmani S, et al., Exploring tumor in diagnosing heterogeneity. Some of the commonly paired radiopharmaceuticals
heterogeneity: The role of PET/CT include F-FDG with Gallium DOTA (1,4,7,10-tetraazacyclododecane-tetraacetic
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with various radiopharmaceuticals 18 68
in diagnosis and treatment acid) peptide for neuroendocrine tumors, F-FDG with Ga-prostate specific
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guidance. Adv Radiother Nucl Med. membrane antigen for prostate cancers, F-metafluorobenzylguanidine with F-
2025;3(2):1-15. FDG and Ga-DOTA peptide for neural crest tumors, and F-fluoroestradiol with
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doi: 10.36922/ARNM025040005 18 F-FDG for breast cancers. Many other tracers, including Ga-fibroblast activation
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Received: January 21, 2025 protein inhibitor and labeled integrins, attach to various components on tumor
Revised: February 19, 2025 cells and TME and have displayed significantly positive effects in certain tumors.
However, their potential role as a biomarker to evaluate tumor heterogeneity and
Accepted: March 5, 2025
its clinical relevance remains largely uninvestigated.
Published online: March 20, 2025
Copyright: © 2025 Author(s). Keywords: Cancer; Heterogeneity; F- FDG; PET/CT
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This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium, 1. Introduction
provided the original work is
properly cited. Cancer development is a multi-step process that undergoes multiple alterations spatially
Publisher’s Note: AccScience and temporally. During its evolution process, heterogeneity develops between various
Publishing remains neutral with cancer cells, displaying distinct characteristics, either within the primary tumor or
regard to jurisdictional claims in 1,2
published maps and institutional among its metastases. Tumor heterogeneity plays a crucial role in cancer management
affiliations. as it directly impacts treatment outcomes and patient prognosis. As we move from
Volume 3 Issue 2 (2025) 1 doi: 10.36922/ARNM025040005