Neuroendocrine Tumors


Somatostatin-Receptor-Scintigraphy ( sstr - Imaging )

Atleast 5 different somatostatin-receptors ( sstr1 - sstr5 ) characterized by clearly differing binding affinities for natural and synthetic somatostatin (analogues) are known up to date.
The receptors are physiologically expressed in various tissues and organs.
1. neuroendocrine cells pancreas, pituitary anterior lobe, thyroid gland, most neuroendocrine tumors (GEP NET)
2. brain, GI-tract, liver, lung, breast brain tumors (e.g. meningeoma), intestinal tumors, liver tumors
3. lymphocytes, leucocytes lymphomas
Somatostatin-receptor-scintigraphy ( Octreoscan, SRI )

whole body scans using SPECT-technique by means of ~ 200 MBq of a somatostatin analogue (111-In-DTPA-octreotide, 111-Indium-DOTA, Nal3-Octreotid / DOTANOC ) for visualisation of somatostatin-receptors (sstr's) 2h, 24h and 48h after iv- injection of ~10 µg of the peptide.

1. planar scintigraphy
2. SPECT : (single photon emission computed tomography)

By means of a rotating gamma camera various slices of specific thickness may be calculated on a computer with imaging regions of interest visualized horizontally and vertically (sagittal).

Imaging may be performed on an outpatient basis (costs !)

Normal: imaging of liver, spleen, thyroid, pituitary gland
kidney and bladder by glomerular filtration, intestine and gallbladder by hepatobiliary elimination
Pathological: most endocrine pancreatic tumors except the majority of insulinomas, carcinoid tumors and pituitary tumors, medullary thyroid carcinoma (MTC)
oncological disease: SCLC, breast cancer, malignant lymphomas, brain tumors, primary liver cell carcinoma (HCC)

sstr-imaging represents a valuable localisation procedure for small neuroendocrine tumors - e.g.gastrinoma; carcinoids.

important indication: all malignant neuroendocrine tumors with metastases, preferentially "non-functioning" GEP-NET during the course opf therapeutic strategy planning.

Due to the specific receptor - expression of most insulinomas SRI does not play a significant role in the localisation of insulinoma, except specific indications in patients with the rare malignant insulinoma

PET (positron emission tomography)

PET is comparable to scintigraphy using radioactive tracers in order to visualize metabolic events in certain tissues. The use of 18-FDG-PET with fluorized deoxyglucose enables visualization of unspecifically increased glucose metabolism seen also in many tumors.

A more specific visualization of neuroendocrine tumors should be easily available in the near future by combination of a somatostatin analogue and PET = DOTATOC-PET.

In some centers simultaneous investigation by means of a CT (computed tomography) and PET enables image fusion (PET-CT) allowing to locate positive signals of the PET in specific structures of the CT.

Radionuclide-, Radiopeptide-Therapy (DOTATOC, DOTANOC, DOTATATE)

Emitters of radioactive gamma- or beta radiation - Yttrium-90, Indium-111, Gallium-68, Lutetium-177 - may be coupled to somatostatin analogues like octreotide (octreotate) via chemical conjugators (DOTA).

In near future therapy by means of 177-Lutetium-DOTATOC or 177-Lutetium-DOTANOC seems to become the standard of radiopeptide-therapy due to advantages of this gamma radiation emitter in contrast to the standard 90-Yttrium-Dotatoc-therapy.

Depending upon the presence of somatostatin-receptor positive tumor tissue endogenous local radiation may be applied - radiopeptide therapy. Especially metastases outside the liver - normally not accessible other than by systemic aggressive chemotherapy, may be reached with this type of therapy.

The procedure in general is comparable to the known and established radio-iodine therapy of thyroidal disease. Instead of the specifically enriched iodine in the thyroid the peptide - somatostatin or its synthetic analogues - is used for which specific receptors have been detected by means of an octreotide scan or complex combined nuclear PET studies.

DOTA: = Tetra-aza-cyclo-dodecane-tetraacetic acid
DOTA-Phe1-Tyr3-Octreotide: DOTATOC
DOTA-Nal3-Octreotide: DOTANOC (Naphythyl-alanine conjugate with octreotide)
DOTA-Thy3-Thre8-Octreotide: DOTATATE

This promising form of therapy is under clinical evaluation and being applied in a few centers in Europe and the US, but already on the verge of becoming a standard therapy for diffusely metastasized NET due ot the clear underlying rationale..