NET / Carcinoid
What are neuroendocrine tumours?
Neuroendocrine cells for the production of various hormones are to be found in every human body. The necessary cell renewal leads to a process of cell division at specific time intervals. This cell division can lead (for example in a weakened immune system) to the malformation of new cells, which as a result of altered genetic information divide more frequently and thus by suppressing healthy cells develop into a neuroendocrine tumour. In contrast to other forms of tumour (carcinomas), neuroendocrine tumours mostly have a significantly slower growth behaviour.
Often, neuroendocrine tumour cells also develop hormones (e.g. serotonin). The resulting pattern of symptoms (carcinoid syndrome) can be: reddening of the head and neck area (flush), diarrhoea, alcohol intolerance, skin changes, asthma-like complaints.
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Diagnosis
Nuclear medicine diagnosis of neuroendocrine tumours
Since its beginnings more than half a century ago, nuclear medicine diagnosis has served for the measurement of organ functions and the imaging of physiological and pathophysiological changes in vivo. The basis for receptor scintigraphy as a molecular imaging procedure is the recognition that a series of cell membrane receptors, which are autoradiographically detectable by means of gamma-emitting radionuclides such as 123Iod, 111Indium, 67Gallium and 99mTechnetium, and more recently by means of positron emitters (68Gallium, 86Yttrium) can be non-invasively detected.
Abstract
Somatostatin receptor scintigraphy (SMRS) specifically detects neuroendocrine tumours (NET) and receptor-positive metastases with high sensitivity (80 to >95%) and allows whole body diagnosis with one scintigraphic examination.
Even small primary tumours and metastases, which are difficult to diagnose with CT, MRI, or sonography, can be detected if the receptor density is high.
If there is strong suspicion of a GEP tumour, or if a NET has been proven by immunohistochemistry, SMRS should be the first diagnostic procedure for staging (before CT and MRI).
Further indications are follow-up after operation and diagnosis of recurrences in cases of increasing specific tumour markers, evaluation of the therapeutic response after chemotherapy or biotherapy, and differential diagnosis of neuroendocrine tumour vs. non-endocrine tumour in cases of a space-occupying mass if a final diagnosis cannot be obtained by biopsy or operation.
Finally, there is an essential role for somatostatin receptor scintigraphy in the pretherapeutic evaluation (receptor density) before peptide receptor radiotherapy and in the follow-up after treatment.
Keywords:
Neuroendocrine tumours/carcinomas • carcinoid • GEP tumours • Somatostatin receptor scintigraphy • nuclear medicine diagnosis
Authors:
R. P. Baum • M. Hofmann
Klinik für Nuklearmedizin/PET-Zentrum,
Zentralklinik Bad Berka GmbH
Medizinische Hochschule Hannover
Published in:
Onkologe 2004 • 10:598–610 DOI 10.1007/s00761-004-0716-1
Published online:
4 June 2004 © Springer-Verlag 2004
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Therapy
Peptide receptor radiotherapy (PRRT) of neuroendocrine tumours
Clinical indications and experience with 90Yttrium-labelled somatostatin analoga
Radionuclide-labelled somatostatin analoga such as 111Indium-octreotide (OctreoScan) or 99mTechnetium-ED-DA-HYNIC-TOC (TETOC) have been successfully used for some years in the diagnosis of neuroendocrine tumours.
On account of their favourable biokinetic characteristics (quick and high enrichment in the tumour, rapid blood clearance) and the development of stable procedures for labelling with β-ray emitting radionuclides, these have been increasingly deployed in recent years as radio peptide therapeutics for the additive treatment of neuroendocrine, especially gastro-entero-pancreatic, tumours (so-called peptide receptor radiotherapy, PRRT, or radio receptor therapy, RRT, for short).
Alongside the traditional pillars of oncological therapy (operation, local treatment procedures, chemo-/biotherapy) radionuclide therapy opens up a new option especially for the treatment of patients showing a progression of the disease under treatment with octreotide (or the combination of octreotide plus interferon) or following local therapy procedures such as chemoembolisation or also following ablative procedures (radio frequency ablation, LITT).
Operatively, local or loco-regional operations usually involving a resection of the primary tumour can be carried out with a curative intention, but in the event of the existence of distant metastases the operation is only successful for a limited period.
Since many neuroendocrine tumours show slow growth (low proliferation rate), chemotherapy is often not very effective and in the case of longer-term application is associated with side-effects (low therapeutic breadth).
The same applies to external radiation therapy; it is rarely used e.g. for bonymetastases or for undifferentiated carcinomas with a high proliferation rate (and then mostly palliative). Nuclear medical therapy with open radioactive substances is based on the fact that specific metabolic processes or cell characteristics can be used in a targeted way.
The best known is the treatment of hyperthyreosis and differentiated thyroid carcinomas with radioactive iodine (radio-iodine therapy), which has been established for 60 years and with which millions of patients have been successfully treated worldwide. Radio-iodine therapy is methodologically very similar to receptor therapy, since the take-up of 3 iodine in the cells takes place through specific mechanisms (Sodium/Iodide Symporter=NIS). The existence of specific receptors on the cell surface of neuroendocrine tumours makes possible the precise binding of receptor ligands to the somatostatin receptor.
Somatostatin analoga (so as DO-TA-TOC, DOTA-TATE, DOTA-NOC) are small peptides which can be labelled with radioactive emitters, such as the therapeutic β-emitter 90Yttrium, and following intravenous (or intra-arterial) injection bind to the tumour or the metastasis and irradiate it “from within”, since the radio-pharmaceutical enriches specifically in the tumour (“internal radionuclide therapy”).
Published in:
Der Onkologe 10 · 2004,
by R. P. Baum · J. Söldner · M. Schmücking · A. Niesen
Klinik für Nuklearmedizin/PET-Zentrum,
Zentralklinik Bad Berka
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