Elsevier

The Lancet Oncology

Volume 2, Issue 3, March 2001, Pages 157-164
The Lancet Oncology

Review
Clinical role of positron emission tomography in oncology

https://doi.org/10.1016/S1470-2045(00)00257-6Get rights and content

Summary

Positron emission tomography (PET) is now in routine use in oncology, through the success of metabolic imaging, mainly with fluorodeoxyglucose (FDG). Clear benefit is obtained with FDG PET in the assessment of patients with recurrent or residual disease, especially colorectal cancer and lymphoma. Preoperative staging of non-small-cell lung cancer with FDG PET is of proven benefit. Staging and restaging of patients with melanoma of stage II or greater is useful, and FDG PET has also been successfully used to investigate single pulmonary nodules. Tumour grading has been assessed, especially in the brain, but an important and emerging indication is the evaluation of tumour response with PET. Rapid decline of FDG uptake has been observed in responsive cancers. Further advances are being made with other fluorine-18-labelled and generatorbased PET tracers, the only ones that can be used in units without dedicated cyclotrons.

Section snippets

Technical aspects

PET is an advanced and demanding technique. It is time consuming, and requires substantial expertise and training.

The minimum infrastructure necessary should not be underestimated. A PET centre will have a cyclotron, supporting radiochemistry laboratory space, usually two PET scanners, and a significant number of support staff (cyclotron operators, medical doctors, medical physicists, radiochemists, technicians, modelling experts, management staff, etc). If tracer development is to take place,

Methodology

PET allows for the recording of data in three dimensions. Thin (3–4 mm) tomograms can be recorded and displayed in any plane (mostly coronal, transverse, and sagittal; Figure 1). Whole-body or single-organ studies can be recorded, and the data-acquisition process optimised. Whole-body studies can take up to 60 minutes to obtain and single-organ studies about 20 minutes. With 18 F-FDG studies, the patient is investigated after a few hours' fast, and blood glucose concentration must be measured

2-18 F-fluoro-2-deoxy-D-glucose (FDG)

18 F has become for PET studies what 99mTc has become for conventional nuclear medicine and SPET investigations. Nowadays, 18 F can be produced in a cyclotron fairly easily and in sufficient quantities.The synthesis of 18 F-FDG (an analogue of glucose) is now largely automatic, with a modular approach.18 F-fluoride is converted into an aqueous medium, a glucose precursor (generally mannose triflate) is used to carry out a nucleophilic substitution on a preformed 18 F-krytofix complex, and after

PET FDG imaging in oncology

In general terms, metabolic activity is assumed to be altered in cancer well before structural changes occur. Therefore, detection of a biochemical, metabolic, or flow signal change well before anatomy is altered must be feasible. This assumption, now confirmed by practice, underlines the overall approach to the investigation of patients with FDG PET.

Examination of the response of cancer to treatment should also be possible, and changes in this response should be detectable before any changes

The normal FDG whole-body PET study

It is important to appreciate the normal distribution of FDG in a whole-body study (Figure 2). FDG is actively taken up by the brain (mainly via GluT1 and GluT3), smooth muscle, and myocardium (mainly via GluT1 and GluT4), and by the bone marrow, and it is excreted mainly by the kidneys (GluT2 is also expressed in kidney tissue). Heart uptake is variable and unpredictable and correlates poorly with diet or serum glucose concentrations. The myocardium can appear as a prominent left ventricle

Lung cancer

Lung cancer is the leading cause of cancer mortality. Small-cell lung cancer (25% of cases) and non-small-cell lung cancer (NSCLC) are the main categories. Surgery is the best option for the cure of early NSCLC (adenocarcinoma, the most frequent squamous-cell carcinoma, and large-cell carcinoma). Small-cell lung cancer has spread at presentation in most cases, and surgical options are rare. Accurate staging of this disease is essential,2 and FDG PET has a major role here.

Dwamena and colleagues'

Colorectal cancer

Colorectal cancer is the third most common malignant disease in the more developed countries, and one in two affected individuals will die from this cancer. After initial diagnosis, survival depends on the presence or absence of malignant deposits (mainly in the liver), the extent of bowel-wall invasion, and the presence of involved local or regional lymph nodes. Colonoscopic screening can detect advanced cancer in at-risk patients without symptoms, even when it is undetected by sigmoidoscopy.10

Lymphoma

A recent small-scale study on the cost-effectiveness of FDG PET versus CT in lymphoma confirmed the experience available from many hundreds of patients investigated in the past 5–10 years.24 Most lymphomas are glucose avid, and lesion detection is therefore facilitated, not only in clusters of lymph nodes but also in soft tissue and bone marrow (Figure 4). Initial work began in the late 1980s, and comparisons were done between gallium-67-citrate whole-body scanning and FDG PET. As a result of

Melanoma

In a prospective investigation of 95 patients with stage III or in-transit melanoma with FDG whole-body PET,30 the technique was deemed to be detecting new disease in 20% of patients and changed management in 15%. The sensitivity in this study was 87.3%, with a positive predictive value of 78.6%, which rose to 90.6% when clinical data were added to the interpretation of the FDG study. There was a significant proportion of false-positive findings in this population, but a combined clinical and

Head and neck cancer

There is controversy about the data published in peer-reviewed journals, and the real place of FDG PET in the investigation and management of patients with cancers of the head and neck remains unclear. Only small studies have been published, despite the real potential for improving surgical planning for these patients. Greven and colleagues found that FDG PET was not helpful in 13 patients with clinically occult primary squamous-cell carcinomas,33 and that a substantial number of false-positive

Breast carcinoma

FDG PET has no established role in the investigation of a primary breast tumour at first presentation. Various other conventional and newer techniques (mammography, ultrasonography, and MRI), and also nuclear medicine with methoxy-isobutyl-isonitrile (MIBI) imaging, are available for this purpose. Nor is there any convincing evidence that FDG PET will be useful in staging of a patient at presentation, especially after the success and progress made with the sentinel lymph-node method. FDG PET

Other applications

FDG PET has been used in many other areas of oncology, from tumours of the central nervous system to thyroid carcinomas, gastrointestinal tumours (especially those of the oesophagus and pancreas), and testicular, germ cell, and neuroendocrine tumours. Patients with paraneoplastic syndromes, as well as patients with prostate, renal and hepatocellular malignancies, are being investigated. PET studies have also been carried out in patients with diagnosed AIDS, mainly to distinguish intracerebral

Tumour response monitoring with FDG PET

There is a clear need to assess tumour response soon after the start of treatment,39, 40 and to distinguish responders from non-responders. Successful therapy can be maintained or augmented, and ineffective treatment can be suspended and other options considered. The present strategy of 'wait and see' is in need of an objective reassessment. FDG PET has been applied to monitor, among other responses, those of lung, brain, breast, and colorectal tumours, but there is an urgent need for large

In vivo imaging of drug action and other potential applications of 18 F PET in oncology

New areas of application are bound to appear. These will reflect the progressive development of 18 Flabelled tracers (Table 2), which will be a key factor in the widespread application of these new imaging agents. In vivo human pharmacokinetics of relevant drugs can be investigated quantitatively by labelling of appropriate ligands. One recent study43 underlines the scope of PET in oncology.18 F-labelled fluorouracil was used to demonstrate an increase in the half-life of labelled ligand in

Present limitations and future developments

There are at present significant limitations with the technology of PET imaging. The best technology (the full ring tomograph) is costly and slow. Although whole-body landmarks permit the experienced observer to recognise and localise most abnormalities in the coronal planes, the thin slices obtained in the transaxial and sagittal planes are often noisy and difficult to interpret. To obtain accurate data for tracer quantification, an emission map is recorded over a few minutes per body section

Search strategy and selection criteria

We have made an effort mainly to cite peer-reviewed data with statistical power, meta-analysis studies, and data published in mainstream clinical, cancer, and surgical oncology journals. Data published in the foremost radiology and nuclear medicine journals have also been cited where appropriate, and editorial comments in these journals made use of. Most of the cited references are less than 3 years old. The review also reflects the experience of the authors responsible for a

References (47)

  • SU Berlangieri et al.

    Metabolic staging of lung cancer

    N Engl 3. Med

    (2000)
  • BA Dwamena et al.

    Metastases from non-small cell lung cancer: mediastinal staging in the 1990s – meta-analytic comparison of PET and CT

    Radiology

    (1999)
  • RM Pieterman et al.

    Preoperative staging of non-small-cell lung cancer with positron-emission tomography

    N Engl J Med

    (2000)
  • SS Gambhir et al.

    Decision tree sensitivity analysis for cost-effectiveness of FDG-PET in the staging and management of non-small cell lung carcinoma

    J Nucl Med

    (1996)
  • M Dietlein et al.

    Cost effectiveness of FDGPET for the management of solitary pulmonary nodules: a decision analysis based on cost reimbursement in Germany

    Eur J Nucl Med

    (2000)
  • VJ Lowe et al.

    Prospective investigation of positron emission tomography in lung nodules

    J Clin Oncol

    (1998)
  • DA Lieberman et al.

    Use of colonoscopy to screen asymptomatic adults for colorectal cancer

    N Engl J Med

    (2000)
  • Abdel-Nabi H, Doerr RJ, Lamonica DM, et al. Staging of primary colorectal carcinomas with fluorine-18...
  • THA Arulampalam et al.

    The role of positron emission tomography in the management of colorectal cancer

    Br J Surg

    (2001)
  • D Delbeke

    Oncological applications of FDT PEG imaging: brain tumours, colorectal cancer, lymphoma and melanoma

    J Nucl Med

    (1999)
  • O Ogunbiyi et al.

    Detection of recurrent and metastatic colorectal cancer: comparison with positron emission tomography and computed tomography

    Ann Surg Oncol

    (1997)
  • D Delbeke et al.

    Staging recurrent metastatic colorectal carcinoma with PET

    J Nucl Med

    (1997)
  • FL Flanagan et al.

    Utility of FDG-PET for investigating unexplained plasma CEA elevation in patients with colorectal cancer

    Ann Surg

    (1998)
  • Cited by (256)

    • Evaluation of radiation doses of the <sup>18</sup>FDG PET/CT hybrid imaging in adult and paediatric oncologic patients

      2023, Radiation Physics and Chemistry
      Citation Excerpt :

      This increase in glucose uptake has been clinically exploited for cancer diagnosis and monitoring through the use of 18 Fluoro-2-deoxy-D-glucose (18FDG). The latter is a radiolabeled glucose analogue used in positron emission tomography (PET) imaging (Bomanji et al., 2001; Weiler-Sagie et al., 2010). PET imaging provides information about molecular and metabolic changes.

    • Fluorodeoxyglucose-positron emission tomography as a potential alternative tool for functional diagnosis of glycogen storage disease type I

      2023, Radiology Case Reports
      Citation Excerpt :

      This increased FDG accumulation in our patient's liver was similar to that previously reported in a GSD type Ib patient and GSD type Ia patient [4,5]. FDG-PET localizes tumors by detecting the FDG-6-phosphate accumulation in tumor cells with a deficiency of glucose-6-phosphatase [6]. Considering the mechanism of FDG accumulation in tumor cells, high FDG accumulation in the liver of these GSD type I patients is considered to be caused by impaired glucose-6-phosphate metabolism in hepatocytes.

    View all citing articles on Scopus
    View full text