Nuclear Medicine Spectrum in Neuroendocrine Tumour Management: Molecular-Based Apogee Effectuating Improved Outcomes

Abstract

Nuclear medicine imaging and treatment play a particularly prominent role in the management of Neuroendocrine Tumours (NET), consistently pertaining to the molecular level on the ground of specific properties of neuroendocrine neoplastic cells. NET may be sporadic or appear as part of an inherited syndrome, originate from the diffuse neuroendocrine system and consist of Amine Precursor Uptake and Decarboxylation (APUD) cells; these cells produce and store hormones which account for a broad spectrum of subsequent clinical manifestations. NET cells also characteristically overexpress specific cell membrane peptide receptors like somatostatin receptors (sstr). Clinically non-functional NET contribute further to their relatively common delayed diagnosis.

Histologic assessment with relative immunohistochemical indices, remains the gold standard for NET diagnosis. Measurement of serum or urinary, specific or non-specific, hormonal markers, aids in the diagnostic NET investigation, with high sensitivity, in addition to follow-up and possibly prognostic value. Involved localization modalities include endoscopic ultrasound (ΕUS), computerized tomography (CT), magnetic resonance imaging (MRI) and radionuclide methods.

Nuclear imaging exploits radiopharmaceuticals similar in molecular structure to the tumour-synthesized substances or incorporated into various tumour cellular metabolic processes, to selectively visualize NET. Established scintigraphic studies on primary and metastatic NET imaging, apply radiolabelled synthetic somatostatin (sst) analogues [like indium-111-diethylene triamine pentaacetic acid-octreotide (¹¹¹Ιn-DTPAoctreotide)] to bind on sstr, iodine-131/123 meta-iodo-benzylguanidine (^131/123I-MIBG) to be actively transported and stored within neurosecretory granules of APUD cells as a chemical nor-epinephrine analogue, and pentavalent technetium-99m dimercaptosuccinic acid [^99mTc(V)-DMSA] to be taken up by cells exhibiting accelerated proliferation. Positron emission tomography (PET) or PET/CT studies are also helpful for NET evaluation, by employing ⁶⁸Ga-labelled sst analogues such as [⁶⁸Ga-DOTA⁰,Tyr³]octreotide (⁶⁸Ga-DOTATOC), [⁶⁸Ga-DOTA⁰,Tyr³]octreotate (⁶⁸Ga- DOTATATE) and ⁶⁸Ga-DOTANOC for sstr binding, ¹⁸F-DOPA, ¹¹C-5-HTP and ¹¹Chydroxyephedrine (¹¹C-HED) for APUD mechanism exploitation, and ¹⁸F-FDG-PET for NET of low-differentiation and high proliferative activity. The traditional whole-body bone scan with ^99mTc-methylene diphosphonate (^99mTc-MDP) adds to staging and prognostic data through the identification of skeletal metastases. Altogether, in patients bearing NET, radionuclide imaging provides non-invasive diagnosis, staging, restaging, treatment planning, prediction of therapy response, selection of patients for targeted (radio- or non-radiolabelled) therapy, and follow-up for detection of relapse or disease progression.