Elsevier

The Lancet Oncology

Volume 7, Issue 9, September 2006, Pages 728-734
The Lancet Oncology

Fast track — Articles
Staging of carcinoid tumours with 18F-DOPA PET: a prospective, diagnostic accuracy study

https://doi.org/10.1016/S1470-2045(06)70801-4Get rights and content

Summary

Background

To assess individual treatment options for patients with carcinoid tumours, accurate knowledge of tumour localisation is essential. We aimed to test the diagnostic sensitivity of 6-[fluoride-18]fluoro-levodopa (18F-DOPA PET), compared with conventional imaging methods, in patients with carcinoid tumours.

Methods

In a prospective, single-centre, diagnostic accuracy study, 18F-DOPA PET with carbidopa pretreatment was compared with somatostatin-receptor scintigraphy (SRS), CT, and combined SRS and CT in 53 patients with a metastatic carcinoid tumour. The performance of all imaging methods was analysed for individual patients, for eight body regions, and for the detection of individual lesions. PET and CT images were fused to improve localisation. To produce a composite reference standard, we used cytological and histological findings; all imaging tests, including secondary assessments for newly found lesions; follow-up; and biochemical data. Sensitivities were calculated and compared.

Findings

In patient-based analysis, we recorded sensitivities of 100% (95% CI 93–100) for 18F-DOPA-PET, 92% (82–98) for SRS, 87% (75–95) for CT, and 96% (87–100) for combined SRS and CT (p=0·45 for 18F-DOPA PET vs combined SRS and CT). However, 18F-DOPA PET detected more lesions, more positive regions, and more lesions per region than combined SRS and CT. In region-based analysis, sensitivity of 18F-DOPA PET was 95% (90–98) versus 66% (57–74) for SRS, 57% (48–66) for CT, and 79% (70–86) for combined SRS and CT (p=0·0001, PET vs combined SRS and CT). In individual-lesion analysis, corresponding sensitivities were 96% (95–98), 46% (43–50), 54% (51–58), and 65% (62–69; p<0·0001 for PET vs combined SRS and CT).

Interpretation

If the improved tumour localisation seen with 18F-DOPA-PET compared with conventional imaging is confirmed in future studies, this imaging method could replace use of SRS, help improve prediction of prognosis, and be used to assess patients' response to treatment for carcinoid tumours.

Introduction

Neuroendocrine tumours are a heterogeneous group of slow-growing lesions arising from neuroendocrine cells, of which carcinoid tumours are the most common. These tumours are often located in the abdomen and can produce and secrete a large variety of products because of their intrinsic ability to take up, accumulate, and decarboxylate amine precursors.1 In metastatic disease, these products, such as serotonin and catecholamines, can bypass the first-pass metabolisation and inactivation by the liver and can cause symptoms. Treatment options for carcinoid tumours include curative or debulking surgery, medical treatment with somatostatin analogues, and interferon.2

To assess individual treatment options, accurate knowledge of tumour localisation, biochemical activity, and progression is essential. The initial work-up for patients with carcinoid tumours consists of morphological imaging methods such as CT, combined with functional whole-body imaging with somatostatin-receptor scintigraphy (SRS).3, 4, 5 However, CT and MRI of the abdomen have difficulties in correctly separating tumours and mesenterial metastases from intestinal structures.6, 7, 8 Furthermore, SRS can produce false-negative findings, because of the variable affinity and expression of somatostatin receptors and the restricted resolution of gamma cameras and single-photon-emission tomography (SPECT) methods.9, 10

PET using the catecholamine precursor 6-[fluoride-18]fluoro-levodopa (18F-DOPA) has emerged as a new imaging method for neuroendocrine tumours.6 By contrast with other methods, this procedure is based on the intrinsic property of neuroendocrine tumours to take up amine precursors, such as 18F-DOPA.11, 12, 13, 14, 15 The combination of this specific tracer with the high resolution provided by PET could lead to a clinically relevant improvement in the detection and staging of neuroendocrine tumours. A few small studies6, 16, 17 have shown some potential of 18F-DOPA PET in small and heterogeneous groups of patients with neuroendocrine tumours.

Therefore, the aim of this study was to compare the diagnostic sensitivity of 18F-DOPA PET with that of conventional imaging methods such as SRS and CT, in a large and homogeneous population of patients with carcinoid tumours.

Section snippets

Patients

Eligible patients for this prospective single-centre diagnostic accuracy study included: those who were newly referred to our centre (which serves the northern region of the Netherlands) with a carcinoid tumour, based on clinical or biochemical findings, and at least one abnormal lesion detected on CT, MRI, sonography, or SRS; and those known to have a histopathologically proven carcinoid tumour, who had a clinical indication for restaging, and who had at least one abnormal lesion on

Results

Between October, 2003, and February, 2006, we asked 68 consecutive patients to participate in the study (figure 1); however, three declined PET scanning, and we could not obtain all required information for 12, because of various logistical reasons (eg, no biochemistry or pathology findings, no SRS). Sensitivity was calculated in the remaining 53 patients assessed, of whom 25 were newly diagnosed with carcinoid disease (table 1). The median time between PET and CT was 59 days (range 1–191) and

Discussion

We showed improved diagnostic sensitivity of 18F-DOPA PET in staging and identification of carcinoid tumours, compared with currently applied, standard whole-body imaging with SRS. Compared with the combination of SRS with CT, 18F-DOPA PET detected substantially more individual tumour lesions, more affected body regions, and more lesions per region. The improved lesion detection of carcinoid tumours with 18F-DOPA PET provides a better understanding of the true extent of tumour spread in

References (38)

  • G Kaltsas et al.

    Recent advances in radiological and radionuclide imaging and therapy of neuroendocrine tumours

    Eur J Endocrinol

    (2004)
  • B Kumbasar et al.

    Imaging of neuroendocrine tumors: accuracy of helical CT versus SRS

    Abdom Imaging

    (2004)
  • FH Fahey et al.

    Sensitivity, resolution and image quality with a multi-head SPECT camera

    J Nucl Med

    (1992)
  • WW de Herder et al.

    Somatostatin receptors in gastroentero-pancreatic neuroendocrine tumours

    Endocr Relat Cancer

    (2003)
  • WG Meijer et al.

    Catecholamine-synthesizing enzymes in carcinoid tumors and pheochromocytomas

    Clin Chem

    (2003)
  • AG Pearse

    The APUD cell concept and its implications in pathology

    Pathol Annu

    (1974)
  • IP Kema et al.

    Serotonin, catecholamines, histamine, and their metabolites in urine, platelets, and tumor tissue of patients with carcinoid tumors

    Clin Chem

    (1994)
  • JM Feldman et al.

    Biogenic amines in carcinoid tumors

    Biog Amines

    (1989)
  • H Ahlstrom et al.

    Pancreatic neuroendocrine tumors: diagnosis with PET

    Radiology

    (1995)
  • Cited by (214)

    • Current status and future prospects of PET-imaging applications in patients with gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs)

      2021, European Journal of Radiology
      Citation Excerpt :

      In accordance to these findings Koopmans et al, in prospective, diagnostic accuracy study showed the superior performance of 18F-FDOPA PET over SRS, CT, and the combination of SRS with CT in staging and detection of low-grade midgut NETs. Based on their findings authors also suggested the omission of 111In-pentetreotide SRS, and the potential employment of 18F-FDOPA PET as the first-line nuclear medicine imaging modality for low-grade GEP-NETs [43]. However, in comparison to STTRs imaging with PET using 68Ga-DOTA-comounds in the setting of low-grade GEP-NETs, 18F-DOPA exhibits inferior performance.

    • New types of localization methods for adrenocorticotropic hormone-dependent Cushing's syndrome

      2021, Best Practice and Research: Clinical Endocrinology and Metabolism
    View all citing articles on Scopus
    View full text