Metabolic positron emission tomography imaging in cancer detection and therapy response
Open accessAbstract
Positron emission tomography (PET) is a noninvasive imaging technique that provides a functional or metabolic assessment of normal tissue or disease conditions. Fluorine 18-fluorodeoxyglucose PET imaging (FDG-PET) is widely used clinically for tumor imaging due to increased glucose metabolism in most types of tumors, and has been shown to improve the diagnosis and subsequent treatment of cancers. We review its use in cancer diagnosis, staging, restaging, and assessment of response to treatment. In addition, other metabolic PET imaging agents in pre-clinical research or clinical trial stages of development are discussed, including amino acid analogs based on increased protein synthesis, and choline, which is based on increased membrane lipid synthesis. Amino acid analogs and choline are more specific to tumor cells than FDG, so they play an important role in differentiating cancers from benign conditions and in the diagnosis of cancers with low FDG uptake or high background FDG uptake. For decades, researchers have shown that tumors display altered metabolic profiles with elevated uptake of glucose, amino acids, and lipids. This can be used for cancer diagnosis and monitoring of the therapeutic response with excellent signal-to-noise ratios.
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Glucose uptake by cancer cells has been successfully exploited via FDG-PET imaging to stage cancers and assess response to therapy.
“Despite challenges associated with targeting glucose metabolism directly, glucose uptake by cancer cells has been successfully exploited in patients through the use of the fluoro-deoxyglucose positron-emission-tomography (FDG-PET) imaging to stage cancers and assess response to therapy (d’Amico, 2015; Farwell et al., 2014; Zhu et al., 2011).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Zhu et al., 2011
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BackgroundInfluentialTherapeutic Strategies Impacting Cancer Cell Glutamine Metabolism
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“The mean uptake value (SUVmean) was calculated within the metabolic volume, which was defined as the volume with uptake larger than 40% of SUVmax (17,28).”
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BackgroundNon-invasive Investigation of Tumor Metabolism and Acidosis by MRI-CEST Imaging
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“The cancer cells showed a sufficiently prevalent that elevated uptake of glucose based on 8F-fluorodeoxyglucose, the cancer diagnosis, and monitoring tool of the therapeutic response [8].”
BackgroundSentinel Lymph Node Biopsy and Complete Lymph Node Dissection for Melanoma
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Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics
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lncRNAs as prognostic markers and therapeutic targets in cuproptosis-mediated cancer
Bhat, A. A., Afzal, M., Moglad, E. H. O., Thapa, R., Ali, H., Almalki, W. H., Kazmi, I. A., Alzarea, S. I., Gupta, G., & Subramaniyan, V. (2024) · Clinical and Experimental Medicine · doi:10.1007/s10238-024-01491-0 · Cited by 46 · see citing works
“This metabolic characteristic has been used diagnostically in positron emission tomography by tagging a radiolabeled glucose analogue [237].”
MethodSchollaert, P., Crott, R., Bertrand, C., D'Hondt, L. A., Borght, T. D. V., & Krug, B. (2014) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-014-2488-2 · Cited by 46 · see citing works
“In the clinical settings, it has become a major clinical diagnostic and prognostic tool, including the prediction of tumor response to neoadjuvant chemoradiation and often leading to appropriate changes in patient management.(6,7) If there is any evidence that sequential (18)FDG-PET may be an early surrogate for patho…”
BackgroundResearch into cancer metabolomics: Towards a clinical metamorphosis
Olivares, O., Däbritz, J. H. M., King, A., Gottlieb, E., & Halsey, C. (2015) · Seminars in Cell and Developmental Biology · doi:10.1016/j.semcdb.2015.09.008 · Cited by 45 · see citing works
“Developed in 1978, FDG can be taken up by glycolytic cells and phosphorylated intracellularly by hexokinase, but as it lacks a 2' hydroxyl group needed for subsequent metabolism, it is retained in the cells in its phosphorylated form [21].”
BackgroundMultimodal Imaging of Pathologic Response to Chemoradiation in Esophageal Cancer
Fang, P. Q., Musall, B. C., Son, J. B., Moreno, A. C., Hobbs, B. P., Carter, B. W., Fellman, B. M., Mawlawi, O. R., Ma, J., & Lin, S. H. (2018) · International Journal of Radiation Oncology*Biology*Physics · doi:10.1016/j.ijrobp.2018.02.029 · Cited by 45 · see citing works
Preclinical models and technologies to advance nanovaccine development
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Cisplatin Resistance and Redox-Metabolic Vulnerability: A Second Alteration
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“Due to this difference in energy metabolism between tumor and normal tissue, uptake of glucose analogs (fluoro‐ deoxy‐glucose) has been utilized successfully in the development of a diagnostic imaging technique, fluoro‐deoxy‐glucose positron emission tomography (FDG‐PET) for cancer de‐ tection [17].”
MethodThe Potential of Metabolic Imaging
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“The sensitivity of [(18)F]-FDG imaging for diagnosing signet ring cell carcinoma and mucinous adenocarcinoma is low (20, 21) because the expression levels of glucose transporter 1 (GLUT-1) in signet ring cell carcinoma and mucinous carcinoma are relatively low (22).”
BackgroundWen, W., Piao, Y., Xu, D., & Li, X. (2021) · Contrast Media & Molecular Imaging · doi:10.1155/2021/7528971 · Cited by 43 · see citing works
Repurposing of Chronically Used Drugs in Cancer Therapy: A Chance to Grasp
Hijazi, M. A., Gessner, A., & El‐Najjar, N. (2023) · Cancers · doi:10.3390/cancers15123199 · Cited by 42 · see citing works
“Interestingly, due to increased glucose metabolism in most tumors, positron emission tomography (PET), a non-invasive imaging technique that utilizes 18F-fluorodeoxyglucose to provide a functional or metabolic assessment of normal tissue or disease conditions, can and has been used for cancer diagnosis and monitoring…”
BackgroundMetabolic reprogramming: a bridge between aging and tumorigenesis
Drapela, S., Ilter, D., & Gomes, A. P. (2022) · Molecular Oncology · doi:10.1002/1878-0261.13261 · Cited by 41 · see citing works
Yu, L., Hu, Q., & Gu, J. (2019) · Pathology & Oncology Research · doi:10.1007/s12253-019-00708-y · Cited by 41 · see citing works
Advances in [18F]Trifluoromethylation Chemistry for PET Imaging
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“The most widely and frequently us d PET radiotr cer by far is glucose 2‐[18F]fluoro‐2‐deoxy‐ ‐glucose ([18 [18 is particularly useful in measuring e hanced glucose metabolism due to alt red energy metabolism, also ferred to as the Warburg effect, i m y cancers [20].”
BackgroundStrategies on Nanodiagnostics and Nanotherapies of the Three Common Cancers
Leng, F., Liu, F., Yang, Y., Wu, Y., & Tian, W. (2018) · Nanomaterials · doi:10.3390/nano8040202 · Cited by 36 · see citing works
“PET/CT has relatively high specificity and accuracy for lung cancer imaging compared with PET alone, and has additional value in detecting extrathoracic metastasis, such as metastasis in the liver [3,4].”
BackgroundPeng, Y., Bi, L., Guo, Y., Feng, D. D., FULHAM, M. J., & Kim, J. (2019) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/embc.2019.8857666 · Cited by 36 · see citing works
Optical and Magnetic Resonance Imaging Using Fluorous Colloidal Nanoparticles
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Wållberg, H., Grafström, J., Cheng, Q., Lu, L., Ahlzén, H.-S. M., Samén, E., Thorell, J.-O., Johansson, K., Dunås, F., Olofsson, M. H., et al. (2012) · Journal of Nuclear Medicine · doi:10.2967/jnumed.111.102194 · Cited by 34 · see citing works
“With the rapidly expanding use of 18FFDG PET for detecting lesions with aberrant metabolic rates (36), the availability of PET centers with cyclotrons (and cyclotron-produced radionuclides) has increased, and clinical applications of positron-emitting nuclides have widened.”
BackgroundImaging joint infections using D-methyl-11C-methionine PET/MRI: initial experience in humans
Polvoy, I., Seo, Y., Parker, M. F. L., Stewart, M. N., Siddiqua, K., Manacsa, H. S., Ravanfar, V., Blecha, J. E., Hope, T. A., VanBrocklin, H. F., et al. (2022) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-022-05858-x · Cited by 32 · see citing works
Recent Advances in the Development and Application of Radiolabeled Kinase Inhibitors for PET Imaging
Bernard‐Gauthier, V., Bailey, J. J., Berke, S., & Schirrmacher, R. (2015) · Molecules · doi:10.3390/molecules201219816 · Cited by 32 · see citing works
Ilter, D., Drápela, S., Schild, T., Ward, N. P., Adhikari, E., Low, V., Asara, J. M., Óskarsson, T., Lau, E. K., DeNicola, G. M., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102627 · Cited by 32 · see citing works
“These differences have been used to diagnose tumors, such as the use of 18F-fluorodeoxyglucose PET imaging [6], and have been considered a hallmark of cancer [7].”
MethodTosi, D., Pieropan, S., Cattoni, M., Bonitta, G., Franzi, S., Mendogni, P., Imperatori, A. S., Rotolo, N., Castellani, M., Cuzzocrea, M., et al. (2021) · Clinical Nuclear Medicine · doi:10.1097/rlu.0000000000003714 · Cited by 31 · see citing works
Expanding Role for Gallium-68 PET Imaging in Oncology
Kleynhans, J., Ebenhan, T., & Sathekge, M. M. (2024) · Seminars in Nuclear Medicine · doi:10.1053/j.semnuclmed.2024.06.001 · Cited by 30 · see citing works
68Ga-labelled NOTA-RGD-GE11 peptide for dual integrin and EGFR-targeted tumour imaging
Chen, C.-J., Chan, C., Lin, K., Chen, J., Tseng, C.-H., Wang, P., Chien, C., Yu, H., & Lin, W. (2018) · Nuclear Medicine and Biology · doi:10.1016/j.nucmedbio.2018.11.003 · Cited by 30 · see citing works
Wong, T. Z., Benefield, T., Masters, S. C., Kiser, J. W., Crowley, J., Osborne, D., Mawlawi, O. R., Barnwell, J., Gupta, P. K., Mintz, A., et al. (2019) · Journal of Nuclear Medicine Technology · doi:10.2967/jnmt.119.228098 · Cited by 30 · see citing works
“Oncologists use PET/CT images to help diagnose and stage disease, choose and plan therapy, and assess tumor response or longitudinally monitor patients (1,18).”
Intercomparison of MR‐informed PET image reconstruction methods
Bland, J., Mehranian, A., Belzunce, M. A., Ellis, S., da Costa-Luis, C. O., McGinnity, C. J., Hammers, A., & Reader, A. J. (2019) · Medical Physics · doi:10.1002/mp.13812 · Cited by 30 · see citing works
“45 Specifically, for brain and neck cancers [ 18 F]FDG PET has played an increasing role in the diagnosis and planning.”
Lin, G., & Chung, Y. (2014) · BioMed Research International · doi:10.1155/2014/625095 · Cited by 31 · see citing works
“Over the past decade, (18)F-FDG PET/CT has become a routine clinical test for staging and restaging of a variety of malignant tumors, including head and neck cancer, lymphoma, colorectal, cervical cancer (Figure 2, [56]), and many other solid organ cancers [48], with a sensitivity of about or above 90% [110].”
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“(8,9) More recently, molecular imaging techniques including positron emission tomography (PET) and single-photon emission computed tomography (SPECT) have also been recognised as valuable tools for evaluating treatment response.(10-13) These imaging techniques allow visualisation and quantitation of cellular and bioch…”
BackgroundMori, M., Passoni, P., Incerti, E., Bettinardi, V., Broggi, S., Reni, M., Whybra, P., Spezi, E., Vanoli, E. G., Gianolli, L., et al. (2020) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2020.07.003 · Cited by 29 · see citing works
“PET images have been garnering more interest because the intensity heterogeneity is expected to be directly associated to tumor biology [14,15] and few studies tried to explore the pancreatic cancer scenario [16-18].”
BackgroundPET Metabolic Biomarkers for Cancer
Croteau, É., Renaud, J. M., Richard, M. A., Ruddy, T. D., Bénard, F., & deKemp, R. A. (2016) · Biomarkers in Cancer · doi:10.4137/bic.s27483 · Cited by 28 · see citing works
Challapalli, A., Barwick, T. D., Pearson, R., Merchant, S., Mauri, F. A., Howell, E. C., Sumpter, K. A., Maxwell, R. J., Aboagye, E. O., & Sharma, R. (2015) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-015-3000-2 · Cited by 28 · see citing works
Fan, W. Q., Shi, W., Zhang, W., Jia, Y., Zhou, Z., Brusnahan, S. K., & Garrison, J. C. (2016) · Biomaterials · doi:10.1016/j.biomaterials.2016.05.036 · Cited by 28 · see citing works
Vaidya, T. P., Agrawal, A., Mahajan, S., Thakur, M. H., & Mahajan, A. (2018) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-018-0367-3 · Cited by 27 · see citing works
Aria, H., Rezaei, M., Nazem, S., Daraei, A., Nikfar, G., Mansoori, B., Bahmanyar, M., Tavassoli, A., Vakil, M. K., & Mansoori, Y. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.947885 · Cited by 26 · see citing works
Application of Metabolic PET Imaging in Radiation Oncology
Zhu, A., Marcus, D. M., Shu, H. G., & Shim, H. (2012) · Radiation Research · doi:10.1667/rr2702.1 · Cited by 27 · see citing works
“Radiotherapy is mainly applied in three areas: (1) adjuvant radiation therapy after breast surgery, (2) radiation therapy for isolated recurrence after surgery, and (3) radiation therapy for metastatic disease.”
BackgroundMethodSelf-citationVisualization, imaging and new preclinical diagnostics in radiation oncology
Cyran, C. C., Paprottka, P. M., Eisenblätter, M., Clevert, D., Rist, C., Nikolaou, K., Lauber, K., Wenz, F. K., Hausmann, D., Reiser, M. F., et al. (2014) · Radiation Oncology · doi:10.1186/1748-717x-9-3 · Cited by 27 · see citing works
“[118-120].”
Exploitation of CD133 for the Targeted Imaging of Lethal Prostate Cancer
Glumac, P. M., Gallant, J. P., Shapovalova, M., Li, Y., Murugan, P. J., Gupta, S., Coleman, I. M., Nelson, P. S., Dehm, S. M., & LeBeau, A. M. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-19-1659 · Cited by 27 · see citing works
“[(18)F]fluorodeoxyglucose ([(18)F]FDG) is commonly used in the clinic to image types of cancer that are dependent on glucose metabolism (15).”
BackgroundVaidya, T. P., Agrawal, A., Mahajan, S., Thakur, M., & Mahajan, A. (2018) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-018-0366-4 · Cited by 26 · see citing works
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“Aerobic glycolysis is an essential feature of tumours, which are different from normal tissue, as demonstrated by the widespread use of positron emission tomography scanning to diagnose cancer cells with active glucose uptake [38].”
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Novel Approaches to Imaging Tumor Metabolism
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What do cellular responses to acidity tell us about cancer?
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Radiolabelling of lipid-based nanocarriers with fluorine-18 for in vivo tracking by PET
Nagachinta, S., Becker, G., Dammicco, S., Navacerrada, M. E. S., Leroi, N., Bahri, M. A., Plenevaux, A., Lemaire, C. F., López‐López, R., Luxen, A., et al. (2020) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2020.110793 · Cited by 24 · see citing works
John, B. V., Aubuchon, S., Dahman, B. A., Konjeti, V. R., Heuman, D. M., Hubert, J., Thomas, S., Deng, Y., Solomon, C., Sundaram, L. T., et al. (2020) · Liver Transplantation · doi:10.1002/lt.25743 · Cited by 23 · see citing works
“Use of [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) with CT for staging has become increasingly common in many cancers due to the ability to detect occult disease, identify metastatic lymphadenopathy, and, in some cases, predict tumor biology and aggressiveness.(3,4) For example, a meta-analys…”
BackgroundMethod
- Authors
- Zhu, A., Lee, D., & Shim, H.
- Affiliations
- Emory University (US)
- Corresponding author
- Shim, Hyunsuk
- Venue
- Seminars in Oncology
- Publisher
- Elsevier BV
- Published
- 2011-02
- Volume
- 38
- Issue
- 1
- Pages
- 55-69
- ISSN
- 0093-7754 (ISSN-L)
- PMC
- PMC3075495
- OpenAlex
- W1982620463
- Cited by
- 368
- References
- 121
- Citations by year
- 2026: 16 · 2025: 31 · 2024: 35 · 2023: 24 · 2022: 35 · 2021: 33 · 2020: 38 · 2019: 36 · 2018: 30 · 2017: 26 · 2016: 17 · 2015: 13 · 2014: 11 · 2013: 11 · 2012: 10
- FWCI
- 8.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Seminars in Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (P50CA128301)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Keywords
- FDG-PET, cancer diagnosis, tumor staging, restaging, treatment response assessment, amino acid analogs, choline PET, tumor glucose metabolism, tumor lipid metabolism, tumor imaging agents
- MeSH terms
- Choline, Humans, Neoplasm Staging, Neoplasms, Sensitivity and Specificity, Tyrosine, Drug Monitoring, Radiopharmaceuticals, Fluorodeoxyglucose F18, Positron-Emission Tomography, Molecular Imaging
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