Positron emission tomography (PET)

During the last few years PET using 18F-labelled deoxy-glucose (FDG) has evolved as a powerful imaging modality in oncology. The recent introduction of PET-CT and also most recently PET-MRI, leads to several advantages over a standard PET. The anatomic localisation will be significantly improved. The positron-emitting radionuclides are generally produced in a low-energy cyclotron and the half-lives are usually short; 2-110 minutes. In practice the use of 11C and 18F-labelled PET tracers requires a cyclotron in the vicinity of the PET camera, but 18F can be transported within radius of about 2 hours. The PET tracers emit positrons which collides with an electron upon which both are annihilated and converted into high-energy photons. These travel in opposite directions and simultaneously reach the detector ring and the line of decay is registered. By collecting data from all detected decays during the acquisition, transaxial images may be reconstructed. The attenuation-corrected PET-images are regularly recalculated to provide images of standardized uptake values (SUVs).

This tracer is not well-designed for well-differentiated NETs with low proliferation capacity. The uptake of the tracer is very low and therefore not of significant clinical value. However, in poorly differentiated highly malignant tumors, FDG-PET might give valuable information for both tumor localisation, characterisation, staging and therapy monitoring.

Specific tracers for NETs are 18F-DOPA PET, 11C-5HTP-PET, 68Ga-DOTA-octreotate. 18F-L DOPA and 11C-L-DOPA has been used in a number of studies to visualize NETs with a sensitivity of somewhere between 50-70%. 18F-DOPA PET has also been informative in the visualization of medullary thyroid cancer. 11C-5-HTP-PET is more sensitive than 11C-L-DOPA and also 18F-DOPA-PET particularly in endocrine pancreatic tumors. In a comparative study between CT-scan, SRS and 5-HTP-PET the latter shows significant higher sensitivity and could also demonstrate more lesions than the other methods. The draw-back with this technique is that it is only available in very few centers, such as Uppsala and Gronningen. The technique can demonstrate tumors down to 3 mm. (Fig. 5, 6)

68Ga-DOTA-octreotate-PET (Fig. 7)
68Ga is a generator-produced positron emitter, which has come more and more in to clinical praxis and is also called “the poor mans PET”. In several studies it demonstrated higher sensitivity than SRS and can be done in “one-stop” procedure. The better spatial resolution by PET speaks in favour of functional imaging by PET compared with SPECT and planar imaging with SRS.

Peptide receptor radionuclide treatment (PRRT)
Peptide radio-receptor radionuclide therapy with radiolabelled somatostatin analogs is an emerging and convincing treatment modality for patients with unresectable somatostatin receptor positive NETs. The somatostatin receptor is strongly over-expressed in most tumors, resulting in high tumor-to-background ratios. In earlier studies 111Indium-DTPA-octreotide were used at high doses for treatment of GEP-NETs, but the responses to these radioactive compounds were very low. During the last years studies have been performed with 90Yttrium labelled somatostatin analogs and most recently 177Lutetium-DOTA-octreotate. A lot of different studies have been published, unfortunately with different treatment protocols, but in general 25-30% of the patients presented objective responses and up to 40% stabilization of a progressive disease. In general PRRT is regarded as a relatively safe treatment with some haematological and renal toxicity in selected cases. The precise role of PRRT has to be defined in forthcoming randomized clinical trials.