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Nuclear Oncology pp 1–40Cite as

Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors

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Abstract

Neuroendocrine tumors (NETs) originate from neuroendocrine cells ubiquitously distributed throughout the body and occur mainly in the gastrointestinal and bronchopulmonary system. They are rare, are mostly sporadic, and comprise 0.66% of all neoplasia. Their incidence/prevalence is increasing based upon more sophisticated diagnostic strategies. Despite the majority being indolent, they are frequently metastatic at diagnosis. As a consequence their prognosis is often limited.

The European Neuroendocrine Tumor Society (ENETS) diagnostic and prognostic stratification criteria are based on histological typing, differentiation, grading (Ki67), and TNM staging. Although the general application of Ki67 is controversial, it remains embedded in therapeutic decision-making pending the implementation of molecular stratification systems.

Surgery is the only curative option. It is however effective in ~20% given the metastatic status of most lesions. Other therapeutic options include somatostatin analogs, interferon, “targeted” drugs, and peptide receptor radionuclide radiotherapy (PRRT).

NETs present a diagnostic and therapeutic challenge as their clinical presentation is protean, nonspecific, and late with hepatic metastases often present. Imaging plays a fundamental role in diagnosis, staging, treatment selection, and follow-up. Current modalities include morphologic techniques (CT, MRI), transabdominal ultrasound (US), and endoscopic (EUS) and intraoperative US (IOUS). Molecular imaging includes scintigraphy (111In-pentetreotide or 99mTc-HYNIC-Tyr3-octreotide), and, more recently, PET with 68Ga-labeled somatostatin analogs (SSA), 18F-DOPA and [11C]5-HTP; catecholamine metabolism is usually imaged with 123I-metaiodobenzylguanidine. [18F]FDG PET/CT has a prognostic role. A role for somatostatin receptor antagonists (better target/background ratio) as theranostics is currently proposed.

The major unmet needs are the development of more inclusive criteria for therapy monitoring, the validation of the recent PET techniques, and the integration of molecular biologic and metabolic information.

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Abbreviations

[11C]5-HTTP:

[11C]5-Hydroxytryptophan

18F-DOPA:

2-18F-Fluoro-l-3,4-dihydroxyphenylalanine

[18F]FDG:

2-Deoxy-2-[18F]fluoro-d-glucose

5-HIAA:

5-Hydroxyindoleacetic acid, an end-metabolite of serotonin

5-HT:

5-Hydroxytriptamin, also known as serotonin

AADC:

Aromatic L-amino acid decarboxylase

AC:

Atypical carcinoid

ACTH:

Adrenocorticotropin hormone

AJCC:

American Joint Committee on Cancer

APUD:

Amine precursor uptake and decarboxylation

AUC:

Area under the curve

BP:

Bronchopulmonary

CEUS:

Contrast-enhanced ultrasonography

CgA:

Chromogranin A, a tumor-associated marker for neuroendocrine tumors

CT:

X-ray computed tomography

CTC:

Circulating tumor cell

CTGF:

Connective tissue growth factor, also known as CCN2

DOTA:

2-(4-Isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (macrocyclic coupling agent to label compounds of biological interest with metal radionuclides)

DOTANOC:

DOTA-Nal3-octreotide

DOTATATE:

DOTA-Tyr3-Thr8-octreotide

DOTATOC:

DOTA-Tyr3-octreotide

DTPA:

Diethylenetriaminepentaacetic acid

DWI:

Diffusion-weighted magnetic resonance imaging, an MR technique used to detect changes in the distribution of water molecules in selected regions

EANM:

European Association of Nuclear Medicine

EC:

Enterochromaffin

ECL:

Enterochromaffin-like

EDDA:

Ethylenediamine-N,N'-bis(2-hydroxyphenyl)acetic acid

ENETS:

European Neuroendocrine Tumor Society

EPAS1:

Gene encoding for the hypoxia-inducible factor 2-alpha (HIF-2α); the gene is also known as HIF2A

EUS:

Endoscopic ultrasonography

FNAC:

Fine needle aspiration cytology

FSH:

Follicle-stimulating hormone

GEP:

Originated in the gastroenteropancreatic tract

GH-RH:

Growth-hormone releasing hormone

GH:

Growth hormone

GIST:

Gastrointestinal stromal tumor

GLP:

Exendin, a glucagon-like protein

HPF:

High-power field in optical microscopy

HYNIC:

Hydrazidonicotinic acid/Hydrazinonicotinamide

IOUS:

Intraoperative ultrasonography

LCNEC:

Large-cell neuroendocrine carcinoma

LH:

Luteinizing hormone

M:

Metastasis status according to the AJCC/UICC TNM staging system

MAX:

Gene encoding for the myc-associated factor X

MDCT:

Multi-detector X-ray computed tomography

MEN:

Multiple endocrine neoplasia

MIBG:

meta-Iodobenzylguanidine

MRI:

Magnetic resonance imaging

N:

Lymph node status according to the AJCC/UICC TNM staging system

NE:

Neuroendocrine

NEN:

Neuroendocrine neoplasia

NET:

Neuroendocrine tumor

NF1:

Gene encoding for neurofibromin

NIH:

United States National Institutes of Health

NKA:

Gene encoding for Na+/K+ ATPase

NSE:

Neuron-specific enolase

OS:

Overall survival

p53:

Tumor protein p53, also known as cellular tumor antigen p53, phosphoprotein p53, tumor suppressor p53, antigen NY-CO-13, or transformation-related protein 53 (TRP53)

PCC:

Pheochromocytoma

PCR:

Polymerase chain reaction

PET:

Positron emission tomography

PET/CT:

Positron emission tomography/Computed tomograhy

PFS:

Progression-free survival

PGL:

Paraganglioma

PPGL:

Pheochromocytoma and paraganglioma

PRRT:

Peptide receptor radionuclide therapy

PTH-RP:

Parathyroid-hormone related protein

PTH:

Parathyroid hormone

qPCR:

Quantitative PCR

RECIST:

Response evaluation criteria in solid tumors

RET:

Proto-oncogene encoding for a receptor tyrosine kinase

SCLC:

Small-cell lung cancer

SDHB:

Gene encoding for succinate dehydrogenase B

SDHD:

Gene encoding for succinate dehydrogenase D

SEER:

Surveillance, Epidemiology, and End Results, a tumor registry of the National Institutes of Health

SIADH:

Syndrome of inappropriate antidiuretic hormone secretion

SNMMI:

Society of Nuclear Medicine and Molecular Imaging

SPECT:

Single-photon computed tomography

SPECT/CT:

Single-photon computed tomography/Computed tomography

SRS:

Somatostatin receptor scintigraphy

SSA:

Somatostatin analog

SSTR:

Somatostatin receptor

SUV:

Standardized uptake value

SUVmax :

Standardized uptake value at point of maximum

T:

Tumor status according to the AJCC/UICC TNM staging system

TC:

Typical carcinoid

TMEM127:

Gene encoding for a protein that acts as a tumor suppressor

TNM:

AJCC/UICC staging system based on parameters “T” (tumor status), “N” (lymph node status), and “M” (distant metastasis status)

TSC:

Gene encoding for the tuberous sclerosis factor, also known as hamartin

TSH:

Thyroid stimulating hormone

UICC:

Union Internationale Contre le Cancer (International Union Against Cancer)

US:

Ultrasonography

VHL:

von Hippel-Lindau

VIP:

Vasoactive intestinal peptide

VMAT:

Gene encoding for the vesicular monoamine transporter

WDHA:

A syndrome characterized by watery diarrhea, hypokalemia, and achlorhydria

WHO:

World Health Organization

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Authors and Affiliations

  1. Division of Nuclear Medicine, European Institute of Oncology, Via G. Ripamonti 435, 20141, Milan, Italy

    Laura Gilardi & Chiara M. Grana

  2. Molecular Imaging and Therapy Service, Memorial Sloan Kettering Cancer Center, New York, USA

    Lisa Bodei

  3. Wren Laboratories, Branford, CT, USA

    Mark Kidd & Irvin M. Modlin

  4. Regional Center of Nuclear Medicine, University of Pisa, Via Roma 55, 56126, Pisa, Italy

    Duccio Volterrani

  5. Nuclear Medicine and Radiometabolic Units, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

    Giovanni Paganelli

  6. Department of Surgery, Yale School of Medicine, 310 Cedar St, New Haven, New Haven, CT, 06510, USA

    Irvin M. Modlin

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    H. William Strauss

  2. Professor Emeritus, University of Pisa, Pisa, Italy

    Giuliano Mariani

  3. Associate Professor and Director of Nuclear Medicine, University of Pisa, Pisa, Italy

    Duccio Volterrani

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    Steven M. Larson

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Bodei, L. et al. (2016). Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors. In: Strauss, H., Mariani, G., Volterrani, D., Larson, S. (eds) Nuclear Oncology. Springer, Cham. https://doi.org/10.1007/978-3-319-26067-9_18-1

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  1. Latest

    Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors
    Published:
    18 August 2022

    DOI: https://doi.org/10.1007/978-3-319-26067-9_18-2

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    Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors
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    17 October 2016

    DOI: https://doi.org/10.1007/978-3-319-26067-9_18-1

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