Elsevier

Seminars in Oncology

Volume 38, Issue 1, February 2011, Pages 55-69
Seminars in Oncology

Molecular imaging in oncology
Metabolic Positron Emission Tomography Imaging in Cancer Detection and Therapy Response

https://doi.org/10.1053/j.seminoncol.2010.11.012Get rights and content

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.

Section snippets

FDG

FDG, an analogue of glucose, is metabolized similarly to glucose. FDG is transported across cell membranes by glucose transporters and is enzymatically phosphorylated to FDG-6-phosphate, which cannot further undergo glycolysis and becomes metabolically trapped intracellularly, in contrast to glucose-6-phosphate.4 The primary exception to the metabolic trapping is in the liver, where a large concentration of phosphatase enzymes results in dephosphorylation of the FDG-6-phosphate and clearance of

Amino Acid Analogs

Due to increased proliferation requiring active protein synthesis, many types of tumors have increased amino acid uptake and upregulated amino acid transporters. Radiolabeled amino acids and their analogs are another class of tumor imaging agents. They are metabolized similarly to amino acids, which are transported across the cell membranes by amino acid transporter proteins. Sodium-independent amino acid transport system L is a major route for providing cells with large neutral amino acids,

Choline

Choline is a precursor of phosphatidylcholine, which is a major constituent of membrane lipids. Membrane lipid synthesis, as well as protein synthesis, is activated during cell proliferation. Therefore, choline is consumed in large quantities by tumor cells.100 11C-cholin has been introduced as an oncological PET tracer for evaluation of a variety of malignant tumors such as brain tumors, and lung, esophageal, colon, bladder, prostate, and many other cancers.101 11C-choline uptake is

Conclusion

FDG-PET is an excellent imaging tool for the diagnosis of primary tumor, recurrence, and metastasis, staging, restaging, and monitoring treatment response in almost all common tumors. Combined PET/CT, which provides functional and anatomical information together, enhances the capability of PET. This enormous capability of PET in oncology is recognized not only by research scientists and clinicians, but also by CMS, which has approved coverage of FDG-PET applications in the initial and

References (117)

  • M. Yoshimoto et al.

    Radiolabeled choline as a proliferation marker: comparison with radiolabeled acetate

    Nucl Med Biol

    (2004)
  • D.W. Townsend et al.

    A combined PET/CT scanner: the path to true image fusion

    Br J Radiol

    (2002)
  • T.M. Blodgett et al.

    PET/CT: form and function

    Radiology

    (2007)
  • E.M. Rohren et al.

    Clinical applications of PET in oncology

    Radiology

    (2004)
  • P. Som et al.

    A fluorinated glucose analog, 2-fluoro-2-deoxy-D-glucose (F-18): nontoxic tracer for rapid tumor detection

    J Nucl Med

    (1980)
  • H. Shim et al.

    A unique glucose-dependent apoptotic pathway induced by c-Myc

    Proc Natl Acad Sci U S A

    (1998)
  • H. Shim et al.

    c-Myc transactivation of LDH-A: implications for tumor metabolism and growth

    Proc Natl Acad Sci U S A

    (1997)
  • P.L. Pedersen

    Tumor mitochondria and the bioenergetics of cancer cells

    Prog Exp Tumor Res

    (1978)
  • M.E. Juweid et al.

    Positron-emission tomography and assessment of cancer therapy

    N Engl J Med

    (2006)
  • Medicare National Coverage determinations manual c, part 4 (sections 200 - 310.1) Coverage determinations 220.6 – positron emission tomography (PET) scans (effective April 3, 2009)

  • A. Jemal et al.

    Cancer statistics, 2010

    CA Cancer J Clin

    (2010)
  • W.J. Oyen et al.

    Role of FDG-PET in the diagnosis and management of lung cancer

    Expert Rev Anticancer Ther

    (2004)
  • R.A. Schmid et al.

    Staging of recurrent and advanced lung cancer with 18F-FDG PET in a coincidence technique (hybrid PET)

    Nucl Med Commun

    (2003)
  • R.J. Hicks et al.

    The utility of 18F-FDG PET for suspected recurrent non-small cell lung cancer after potentially curative therapy: impact on management and prognostic stratification

    J Nucl Med

    (2001)
  • R.J. Hicks

    Role of 18F-FDG PET in assessment of response in non-small cell lung cancer

    J Nucl Med

    (2009)
  • P. Verboom et al.

    Cost-effectiveness of FDG-PET in staging non-small cell lung cancer: the PLUS study

    Eur J Nucl Med Mol Imaging

    (2003)
  • S.N. Reske et al.

    FDG-PET for clinical useResults of the 3rd German Interdisciplinary Consensus Conference, “Onko-PET III”, 21 July and 19 September 2000

    Eur J Nucl Med

    (2001)
  • S.M. Eschmann et al.

    18F-FDG PET for assessment of therapy response and preoperative re-evaluation after neoadjuvant radio-chemotherapy in stage III non-small cell lung cancer

    Eur J Nucl Med Mol Imaging

    (2007)
  • D. Hellwig et al.

    Diagnostic performance and prognostic impact of FDG-PET in suspected recurrence of surgically treated non-small cell lung cancer

    Eur J Nucl Med Mol Imaging

    (2006)
  • M. Tulchinsky et al.

    Small bowel metastasis from lung cancer detected on FDG PET/CT

    Clin Nucl Med

    (2009)
  • Y. Yamamoto et al.

    Early assessment of therapeutic response using FDG PET in small cell lung cancer

    Mol Imaging Biol

    (2009)
  • L.F. de Geus-Oei et al.

    Chemotherapy response evaluation with 18F-FDG PET in patients with non-small cell lung cancer

    J Nucl Med

    (2007)
  • D. Lardinois et al.

    Staging of non-small-cell lung cancer with integrated positron-emission tomography and computed tomography

    N Engl J Med

    (2003)
  • M. Basely et al.

    Umbilical metastasis from breast cancer detected by FDG PET

    Clin Nucl Med

    (2009)
  • J. Duch et al.

    18F-FDG PET/CT for early prediction of response to neoadjuvant chemotherapy in breast cancer

    Eur J Nucl Med Mol Imaging

    (2009)
  • T.S. Aukema et al.

    A different role for FDG PET/CT in axillary lymph node staging in breast cancer

    Eur J Nucl Med Mol Imaging

    (2009)
  • N.R. Peare et al.

    The use of FDG-PET in assessing axillary lymph node status in breast cancer: a systematic review and meta-analysis of the literature

    Breast Cancer Res Treat

    (2010)
  • O. Belohlavek

    What is the role of FDG-PET in the initial staging of breast cancer?

    Eur J Nucl Med Mol Imaging

    (2008)
  • T.F. Çermik et al.

    Impact of FDG PET on the preoperative staging of newly diagnosed breast cancer

    Eur J Nucl Med Mol Imaging

    (2008)
  • F. Crippa et al.

    FDG-PET for axillary lymph node staging in primary breast cancer

    Eur J Nucl Med Mol Imaging

    (2004)
  • J.S. Sloka et al.

    A quantitative review of the use of FDG-PET in the axillary staging of breast cancer

    Med Sci Monit

    (2007)
  • S. Ueda et al.

    Utility of 18F-fluoro-deoxyglucose emission tomography/computed tomography fusion imaging (18F-FDG PET/CT) in combination with ultrasonography for axillary staging in primary breast cancer

    BMC Cancer

    (2008)
  • N.M.E. Straver et al.

    Feasibility of FDG PET/CT to monitor the response of axillary lymph node metastases to neoadjuvant chemotherapy in breast cancer patients

    Eur J Nucl Med Mol Imaging

    (2010)
  • A. Kumar et al.

    The role of 18F-FDG PET/CT in evaluation of early response to neoadjuvant chemotherapy in patients with locally advanced breast cancer

    Eur Radiol

    (2009)
  • N. Momiyama et al.

    Early prediction of response to primary chemotherapy by sequential FDG -PET in patients with advanced breast cancer

    Nippon Rinsho

    (2007)
  • K. Kitajima et al.

    Performance of integrated FDG PET/contrast-enhanced CT in the diagnosis of recurrent colorectal cancer: comparison with integrated FDG PET/non-contrast-enhanced CT and enhanced CT

    Eur J Nucl Med Mol Imaging

    (2009)
  • Y.Y. Shen et al.

    Clinical impact of 18F-FDG-PET in the suspicion of recurrent colorectal cancer based on asymptomatically elevated serum level of carcinoembryonic antigen (CEA) in Taiwan

    Hepatogastroenterology

    (2006)
  • J. Votrubova et al.

    The role of FDG-PET/CT in the detection of recurrent colorectal cancer

    Eur J Nucl Med Mol Imaging

    (2006)
  • C. Ferme et al.

    Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease

    N Engl J Med

    (2007)
  • M.E. Juweid

    Utility of positron emission tomography (PET) scanning in managing patients with Hodgkin lymphoma

    Hematology Am Soc Hematol Educ Program

    (2006)
  • Cited by (252)

    View all citing articles on Scopus

    Financial disclosures: D.J. Lee: Clinical Investigator for Immunomedics, Inc.

    View full text