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Developments in PET for the detection of endocrine tumours

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Positron emission tomography (PET) supplies a range of labelled compounds to be used for the characterization of tumour biochemistry. Some of these have proved to be of value for clinical diagnosis, treatment follow-up, and clinical research. 18F-fluorodeoxyglucose PET scanning is now a widely accepted imaging approach in clinical oncology, reflecting increased expression of glucose transporters in cancerous tissue. This tracer, however, does not show sufficient uptake in well-differentiated tumours such as neuroendocrine tumours. Endocrine tumours have the unique characteristics of taking up and decarboxylating amine precursors. These so-called APUD characteristics offer highly specific targets for PET tracers. Using this approach, radiopharmaceuticals such as [11C]-5-hydroxytryptophan and [11C]-l-dihydroxyphenylalanine for localization of carcinoid and endocrine pancreatic tumours, 6-[18F]-fluorodopamine and [11C]-hydroxyephedrine for phaeochromocytomas, and [11C]-metomidate for adrenal cortical tumours have been developed. Functional imaging with PET using these compounds is now being employed to complement rather than replace other imaging modalities. Development of new PET radiopharmaceuticals may in the future allow in vivo detection of tumour biological properties, such as malignant potential and responsiveness to treatment.

Section snippets

Positron emission tomography (PET) in oncology

Rapid development in synthetic chemistry has provided a range of new potential tracers for PET. Depending on the tracer utilized, one can selectively measure the function of different metabolic pathways of interest or expression of receptors and enzymes. This approach may also, in addition to diagnosis, offer an opportunity to measure metabolic changes in tumours after treatment.

At present, the routine evaluation of tumour response to treatment has relied on anatomical changes—measured by

Endocrine tumours

Tumours of endocrine origin differ from most other tumours in that their functional characteristics can cause severe clinical syndromes despite small tumour size. Conventional morphological imaging methods may therefore fail to visualize such tumours or their metastases. Novel functional imaging techniques, including PET, now exploit specific characteristics of endocrine tumours for detection and staging, to predict histological features and guide therapy.

Endocrine tumour cells take up hormone

PET principles and tracers

A PET scanning session can take 20–60 minutes or more, depending on the number of body regions which are examined, the isotope employed, the delay between tracer accumulation and data acquisition, scanner configuration, and the nature of data acquisition. Current PET tomographs or PET cameras have a spatial resolution of 5–10 mm. A PET camera looks very similar to a CT scanner with a couch for the patient who, during scanning, is positioned in a short tunnel, which holds the detector rings. The

Carcinoids and endocrine pancreatic tumours

Neuroendocrine tumours are derived from endocrine cells; they usually contain secretory granules and have the capacity to produce biogenic amines and polypetide hormones. Pearse presented the so-called APUD concept based on the observation that certain cells have the capacity to take up and decarboxylate amine precursors such as 5-hydroxytryptophan (5-HTP) and l-dihydroxyphenylalanine (l-DOPA). Tumours derived from these cells were consequently called APUDomas.2, 3

Carcinoids are usually

Phaeochromocytomas

Phaeochromocytomas are tumours derived from chromaffin cells in the adrenal gland. Extra-adrenal phaeochromocytomas are called paragangliomas. Adrenal gland imaging by any modality is not indicated until the clinical and biochemical diagnosis of catecholamine excess is established, so that subsequent imaging procedures can be tailored to the best clinical and scintigraphic advantage.

CT and MRI are usually the initial localizing procedures for adrenal and extra-adrenal tumours, and the

Adrenocortical tumours

As a result of the increased use of CT, MRI and ultrasonography, accidentally detected masses at the site of the adrenals-so-called incidentalomas-are frequently revealed (see Chapter 1). Incidentalomas, reported to occur in 0.3–4.0% of abdominal CT investigations27, are in most instances benign adrenal cortical adenomas without clinical or biochemical manifestations of hormone excess. Some incidentalomas represent phaeochromocytomas, metastases to the adrenal, or are of another adrenal or

Medullary thyroid cancer (MTC)

Approximately 3–5% of all cases of thyroid cancer are MTC. MTC occurs in both sporadic (80%) and familial (20%) forms36, the latter associated with MEN-2a or -2b. Nearly 50% of patients have metastatic nodal cervical disease when they are diagnosed. When the lesion is palpable, surgical cure is rarely achieved despite performance of so-called radical neck dissection, but the 10-year survival rate is 86% even with persistent hypercalcitoninaemia.37 The 5-year survival rates are better for

Primary hyperparathyroidism

In about 90% of cases, primary hyperparathyroidism is caused by a solitary parathyroid adenoma.42 However, in MEN-1, multiple glands are usually involved (hyperplasia or adenoma).

The traditional surgical approach is a bilateral exploration of the neck under general anaesthesia with adenectomy, usually with biopsies from all four glands. Using this procedure, experienced surgeons have a success rate of about 90%.42, 43 For hyperplasia, subtotal parathyroidectomy (3.5 glands) or total

Pituitary tumours

Conventional imaging with MRI and petrosal sinus sampling in Cushing's syndrome are the diagnostic methods of choice for pituitary adenomas.21

A number of PET tracers have been used—mainly for research purposes—in pituitary adenomas, including 11C-methionine, 11C-deprenyl, 11C-raclopride, 11C-methylspiperone for imaging based on the presence of receptors.49, 50, 51 These ligands have been shown to help to discriminate between different types of pituitary adenomas, or between viable tumour tissue

Conclusion

PET imaging for localization is more or less established in different types of endocrine tumours. In the future, the PET technique may enable in vivo determination of proliferation and alterations in gene expression during treatment directly.

References (51)

  • G. Kaltsas et al.

    Comparison of somatostatin analog and meta-iodobenzylguanidine radionuclides in the diagnosis and localization of advanced neuroendocrine tumours

    J Clin Endocrinol Metab

    (2001)
  • H. Örlefors et al.

    Positron emission tomography (PET) with 5-hydroxytryptophan (5-HPT) in the diagnosis and treatment follow-up of carcinoid tumours

    J Clin Oncol

    (1998)
  • H. Ahlström et al.

    Pancreatic neuroendocrine tumours: diagnosis with PET

    Radiology

    (1995)
  • S. Hoegerle et al.

    Whole-body 18F-DOPA PET for detection of gastrointestinal carcinoid tumours

    Radiology

    (2001)
  • B. Eriksson et al.

    PET for clinical diagnosis and research in neuroendocrine tumours

  • C. Pasquali et al.

    Neuroendocrine tumour imaging: can 18F-fluorodeoxyglucose positron emission tomography detect tumours with poor prognosis and aggressive behaviour

    World J Surg

    (1998)
  • K. Pacak et al.

    Recent advances in genetics, diagnosis, localization, and treatment of pheochromocytoma

    Ann Intern Med

    (2001)
  • S. Maurea et al.

    Iodine-131-metaiodobenzylguanidine scintigraphy in preoperative and postoperative evaluation of paragangliomas: comparison with CT and MRI

    J Nucl Med

    (1993)
  • B.L. Shulkin et al.

    PET scanning with hydroxyephedrine: an approach to the localization of pheochromocytoma

    J Nucl Med

    (1992)
  • K. Pacak et al.

    6-[18F]fluorodopamine positron emission tomographic (PET) scanning for diagnostic localization of pheochromocytoma

    Hypertension

    (2001)
  • K. Pacak et al.

    Functional imaging of endocrine tumours: role of positron emission tomography

    Endocr Rev

    (2004)
  • E. Van der Harst et al.

    [(123)I]metaiodobenzylguanidine and [(111)In]octreotide uptake in benign and malignant pheochromocytomas

    J Clin Endocrinol Metab

    (2001)
  • B.L. Shulkin et al.

    Pheochromocytomas: imaging with 2-[fluorine-18] fluoro-2-dexo-d-glucose PET

    Radiology

    (1999)
  • D. Kwekkeboom et al.

    Somatostatin receptor scintigraphy

  • D.J. Kwekkeboom et al.

    Octreotide scintigraphy for the detection of paragangliomas

    J Nucl Med

    (1993)

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