Page 12 - ARNM-3-2

Advances in Radiotherapy
& Nuclear Medicine Role of PET/CT in exploring tumor heterogeneity

other biological processes. 14 18 F-FDG PET scans can intratumoral heterogeneity. For example, endocrine-
quantify voxel-based glucose metabolism within tumors; related cancers, such as thyroid and neuroendocrine tumors
FDG uptake and distribution in a tumor are associated (NETs), exhibit a wide range of clinical behaviors. Well-
with the expression of glucose transporters and hexokinase differentiated tumors tend to be indolent and retain their
within a given lesion, as well as between different sites of endocrine function, while poorly differentiated tumors are
that single tumor. more aggressive. F-FDG PET is particularly effective in
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18 F-FDG PET/CT scans can quantify variations in identifying this aggressive phenotype. Similarly, different
tracer uptake by assessing metabolic parameters, such as molecular subtypes of breast cancer can be targeted with
SUV (SUV ; SUV mean ), metabolic tumor volume (MTV), specific tracers, offering a complete picture of the tumor and
max
and total lesion glycolysis (TLG). These metrics can be its heterogeneity. Prostate cancers tend to be differentiated
combined with other advanced texture features (e.g., or poorly differentiated, with diagnosis performed using
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entropy and uniformity) to capture tumor variability and Ga-PSMA and F-FDG PET scans. In addition, some
heterogeneity. 14 may even exhibit neuroendocrine differentiation, which
can be identified with Ga-DOTA peptide PET scans.
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The potential of F-FDG PET/CT scans in evaluating This approach captures complementary biological features
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the heterogeneity at the tumor level has been explored of the tumor and its microenvironment, enabling a more
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by several authors. It has been described that tumor comprehensive assessment of heterogeneity. Combining
heterogeneity may lead to heterogeneous or sparse these methods can improve the characterization of
18 F-FDG distribution. High SUV regions on F-FDG tumor behavior, predict treatment resistance, and guide
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PET scans are indicative of aggressive clones. Cancers personalized therapy by mapping both metabolic and
of lung, head and neck, and oligodendroglioma have molecular heterogeneity.
revealed a clear relationship between the variability in
FDG distribution with pathological variability. Increased Various PET radiopharmaceuticals used clinically and
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heterogeneity of FDG uptake is associated with reduced in research are shown in Table 1. Herein, we describe
survival, highlighting the prognostic importance of PET some of these tracers, their known combinations, and their
imaging. 16-18 Similarly, in sarcoma and cervical cancers, F- potential applications in various tumors.
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FDG PET uptake and its heterogeneous distribution are also 6.1. Ga-DOTA peptides PET/CT for NET
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known to correlate with prognosis and patient outcomes.
Variations in FDG uptake within these tumors can Tumor heterogeneity is seen commonly in NET. NET
provide valuable insights into aggressiveness and potential overexpresses somatostatin receptors (SSTRs); PET/CT
behavior with higher variation in SUV uptake, indicating with 68 Ga-DOTA peptide (DOTATATE/DOTANOC/
more aggressive tumor biology and poorer prognosis. DOTATOC) reflects somatostatin receptor expression in
Therefore, the future focus of F-FDG PET scanning is to the tumor and identifies cell differentiation and grade of
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utilize this information on tumor heterogeneity to enhance the tumor. High Ga-labeled peptide binding is correlated
precise treatment planning and diagnosis. 19-21 with well-differentiated, low-grade lesions, while reduced
binding implies poorly differentiated tumors or higher-
Furthermore, this heterogeneity information is grade tumors. F-FDG PET is sometimes coupled with
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instrumental in radiotherapy planning. By identifying 68 Ga-labeled peptide scans, as FDG accumulation is related
regions within the tumor that exhibit higher metabolic to the metabolic activity of the tumor, displaying higher
activity, clinicians can tailor radiotherapy treatments to sensitivity for poorly differentiated, aggressive tumors with
target these areas more effectively, potentially improving poor outcomes. The phenomenon observed between
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treatment efficacy and minimizing damage to surrounding the two tracers reveals substantial metabolic and receptor
healthy tissue. This tailored approach aims to enhance heterogeneity. These methodologies enable doctors
treatment effectiveness and reduce harm to neighboring to evaluate inter-lesion variability, with differences in
healthy tissue, ultimately contributing to better patient uptake between primary and metastatic locations, directly
outcomes. 22,23 influencing therapy eligibility, such as patient selection
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6. Beyond F-FDG: Commonly used paired for somatostatin receptor therapy (SSRT). Peptide
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receptor radionuclide therapy (PRRT) is radionuclide
specialized PET tracers in different cancers therapy for NET, which is positive in Ga- DOTA peptide
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In addition to F-FDG, various PET tracers have been PET/CT scans and displays minimal or no uptake in F-
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developed over time to target different tumor components. FDG PET/CT scans. Therefore, combining DOTA peptide
The distribution and uptake of these tracers provide a PET/CT scans with other tracers, most commonly FDG
comprehensive, non-invasive map of both inter- and PET scans, can diagnose heterogeneous clones of tumors
Volume 3 Issue 2 (2025) 4 doi: 10.36922/ARNM025040005