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

Table 1. (Continued)
PET radiopharmaceutical Mechanism of localization Oncological indication
18 F-ICMT-11 Binds in caspase 3-specific cells Identification of treatment-induced
undergoing apoptosis apoptosis and response to treatment in
124 I -annexin V Binds to phosphatidyl serine on the malignant tumors
surface of apoptotic cells
18 F-sodium fluoride (NaF) Deposits in bone through chemisorption, Detection of bony metastases
converting hydroxyapatite to fluorapatite
68 Ga-pentaxifor Targets cells exhibiting CXCR 4 Diagnosis of multiple myeloma and other
expression tumors
68 Ga-DOTA exendin-4 Amino acid peptides, like GLP 1, bind to Diagnosis of insulinoma
GLP receptors on pancreatic beta cells
18 F-fludarabine Purine analog that inhibits DNA Diagnosis of hematological malignancies
synthesis
68 Ga-glypican 3 Oncofetal acetyl heparan sulfate Diagnosis of HCC
glycoprotein expressed on HCC
Abbreviations: CXCR4: Chemokine receptor type 4; DNA; Deoxyribonucleic acid; DOPA: 1,4,7,10-Tetraazacyclododecane-tetraacetic acid;
DOTA: 1,4,7,10-Tetraazacyclododecane-tetraacetic acid; 18 F-ICMT -11: (18F-(S)-1-((1-(2-fluoroethyl)-1H-[1,2,3]-triazol-4-yl) methyl)-5-(2
(2,4-difluorophenoxymethyl)-pyrrolidine-1-sulfonyl) isatin); ER: Estrogen receptors; EGFR: Epidermal growth factor receptor; FAP: Fibroblast
activation protein; GLP-1: Glucagon-like peptide 1; GLUT: Facilitated diffusion Glucose Transporters; HCC: Hepatocellular carcinoma; HER2: Human
epidermal growth factor receptor 2; PD-L1: Programmed cell death ligand-1; PSMA: Prostate specific membrane antigen; RGD: Peptide Arg-Gly-Asp;
VEGFA; Vascular endothelial growth factor A.

and guide treatment strategies. Kaewput et al. have Iodobenzylguanidine [1231-MIBG]). These tracers
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demonstrated that 68 Ga-DOTA peptide and 18 F-FDG exhibit variable uptake capacities in tumors, aiding in
PET scans serve complementary roles in patients with diagnosis and therapeutic management. These tumors
gastroenteropancreatic (GEP) NET, simultaneously accumulate amino acids and amine precursors. F-DOPA
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enhancing diagnostic accuracy due to the heterogeneity is a radiolabeled amino acid that enters the tumor cell
of lesions. Similarly, many authors, including Zhou et al., through the L-amino acid transporter (LAT1 and LAT2).
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have revealed that dual tracer PET with Ga-DOTA In the cells, F-DOPA is decarboxylated to dopamine and
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peptide and F-FDG PET should be performed in all transported and stored inside secretory vesicles. Cancer
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patients with an initial diagnosis of NET due to the cells have increased synthesis and storage of amines, like
heterogeneous nature of these tumors. Nogareda Seoane dopamine; therefore, PET imaging with DOPA enables
et al. demonstrated that Ga-DOTA peptide and F-FDG the diagnosis of these tumor cells. This renders PET
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PET scans collectively reveal the molecular heterogeneity imaging with F-DOPA remarkably helpful for diagnosing
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of metastatic lesions in G2 and G3 NET, facilitating the neuroblastoma and other neural crest tumors, as well
appropriate selection of patients for radionuclide therapy as congenital hyperinsulinemia. Neural crest tumors
(PRRT). Dual tracer PET imaging with F-FDG and frequently overexpress norepinephrine transporters, that
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68 Ga-DOTA peptide demonstrating tumor heterogeneity is is, proteins that facilitate the uptake of norepinephrine,
displayed in Figure 1. epinephrine, and dopamine across cell membranes.
18 F-MFBG is a norepinephrine analog that can be targeted
6.2. PET/CT in neural crest tumors to diagnose neural crest tumors. These PET tracers have
PET/CT with various radiopharmaceuticals is remarkably varied uptake capacities in tumor sites depending on their
effective for imaging a group of tumors arising from biological characteristics, demonstrating heterogeneity
the neural crest, including medullary thyroid cancers, that helps refine oncology diagnosis and treatment
neuroblastoma, paraganglioma, pheochromocytoma, strategies. 13,31 In a study, involving the evaluation of
and ganglioneuroma. These tumors express different recurrent and metastatic paraganglioma with different
amines and peptides that can be targeted by various PET PET tracers, authors found that 68 Ga-DOTA-1-Nal3-
tracers, such as F-dihydroxyphenylalanine ( F-DOPA), octreotide (DOTANOC) PET/CT displayed more bone
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68 Ga-DOTA peptides, 18 F-FDG, and other tracers lesions, while F-3,4- dihydroxy-6-[ F]fluoro (FDOPA)
(norepinephrine analog F- metafluorobenzylguanidine PET was superior in detecting liver lesions, demonstrating
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[MFBG], resembling single photon emission the heterogeneous nature of tumor lesions being detected
computed tomography [SPECT] tracer 123 Iodine-Meta- variably by different PET tracers. Similarly, in a study on
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Volume 3 Issue 2 (2025) 6 doi: 10.36922/ARNM025040005