Neuroendocrine tumours

Neuroendocrine tumours (NETs) are a heterogeneous group of neoplasms that originate from neuroendocrine cells, and are often small and can be situated almost throughout the body. Somatostatin receptor scintigraphy (SNS) is a standard procedure for the detection of NETs.

SSTR targeting

NETs typically overexpress somatostatin receptors (SSTRs). These receptors are used as targets for radiopharmaceuticals for both NET detection and therapeutics. 111In-labelled SSTR2 ligand DTPA-octreotide ([111In]pentetreotide) is routinely used SPECT radiopharmaceutical for NET detection. Several 68Ga-labelled SSTR radioligands have been introduced for PET imaging (Fani et al., 2017). However, SSTR imaging is not specific to NETs; for example some lymphomas express SSTRs (Ruuska et al., 2018).

Non-functional pancreatic neuroendocrine neoplasms (PNENs) usually express SSTR2, and commonly also other subtypes, except that the expression of SSTR4 was rare; SSTR5 expression may suggest better prognosis (Majala et al., 2022). [18F]SiTATE is highly selective for SSTR2 with only minor affinity to the SSTR3 and SSTR4 and nearly no affinity to the SSTR subtype 1 and 5.

Peptide receptor radionuclide therapy (PRRT) with 177Lu-carrying somatostatin analogues, such as [177Lu]dotatate (Strosberg et al., 2017), is routinely used in treatment of inoperable NETs. Kidneys and bone marrow are the dose-limiting organs for PRRT. Co-administration of an amino acid solution containing L-lysine and L-arginine with PRRT markedly reduces renal toxicity.

Monoamine system

Because of their neuroendocrine origin, NETs take up amino acids and convert them into biogenic amines (dopamine and serotonin) by decarboxylation and store the amines in vesicles. The alternative term APUDoma refers to this concept of 'Amino Precursor Uptake and Decarboxylation'. L-DOPA is a precursor of catecholamines (dopamine, noradrenalin, adrenalin). Decarboxylation of L-DOPA into dopamine is catalysed by the aromatic amino acid decarboxylase (AADC).

Active uptake and decarboxylation of L-DOPA leads to avid uptake of L-DOPA analogue [18F]FDOPA, which is commonly used in PET imaging of NETs (Becherer et al., 2004). Islet cells in pancreas take up L-DOPA (Borelli et al., 1997), and Ahlström et al (1995) utilized this to visualize pancreatic NETs using [11C]L-DOPA. Bergström et al (1996) demonstrated that the increased uptake of [11C]L-DOPA was due to decarboxylation. Whole body [18F]FDOPA PET was found to detect gastrointestinal carcinoid tumours, and localized the primary tumours; serotonin expressing tumours were found to be especially avid for [18F]FDOPA uptake (Hoegerle et al., 2001a). [18F]FDOPA was found to detect medullary thyroid carcinomas better than SNS or [18F]FDG (Hoegerle et al., 2001b). [18F]FDOPA PET may not be optimal for imaging of small cell lung carcinoma (SCLC), although these carcinomas express neuroendocrine markers (Jacob et al. 2003). [18F]FDOPA whole-body PET is highly sensitive and specific for detection of pheochromocytomas (Hoegerle et al., 2002). [18F]FDOPA PET of pancreas has also been shown to distinguish between focal and diffuse forms of hyperinsulinism (HI) in infancy (Ribeiro et al. 2007).

[11C]-5-hydroxytryptophan ([11C]-5-HTP) is specifically taken up by carcinoid serotonin-producing tumours, decarboxylated by AADC, and stored in vesicles as [11C]serotonin. [11C]-5-HTP provided in some cases higher SUV than [18F]FDOPA (Ahlström et al. 1995), and was shown to be more sensitive in imaging small NET lesions (Örlefors et al. 2005). Contrast of the [11C]-5-HTP uptake images could be further enhanced by concomitant administration of AADC inhibitor carbidopa. 6-[18F]Dopamine ([18F]DA) has been shown to be highly sensitive and superior to SNS (Pacak et al., 2001; Ilias et al., 2003).

See also:


Hope TA, Allen-Auerbach M, Bodei L, Calais J, Dahlbom M, Dunnwald LK, Graham MM, Jacene HA, Heath CL, Mittra ES, Wright CL, Fendler WP, Herrmann K, Taïeb D, Kjaer A. SNMMI Procedure Standard/EANM Practice Guideline for SSTR PET: Imaging Neuroendocrine Tumors. J Nucl Med. 2023; 64(2): 204-210. doi: 10.2967/jnumed.122.264860.

Minn H, Kauhanen S, Seppänen M, Nuutila P. 18F-FDOPA: a multiple-target molecule. J Nucl Med. 2009; 50: 1915-1918. doi: 10.2967/jnumed.109.065664.

Wong RKS, Metser U, Veit-Haibach P. Neuroendocrine tumours: imaging perspective. PET Clin. 2021; 16: 353-364. doi: 10.1016/j.cpet.2021.03.002.

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Updated at: 2023-02-10
Created at: 2016-03-18
Written by: Vesa Oikonen