Fanti / Nanni / Baum PET Imaging in the Management of Neuroendocrine Tumors, An Issue of PET Clinics

1. Auflage 2014
ISBN: 978-0-323-26405-1
Verlag: Elsevier HealthScience EN
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, Band Volume 9-1, 100 Seiten

Reihe: The Clinics: Radiology

Nuclear Medicine has greatly contributed to the diagnosis and treament of neuroendocrine neoplasms. This issue of PET Clinics will focus not only on the diagnosis and treatment of neuroendocrine tumors, but also theranostics. Topics include SPECT and other PET tracers, F-DOPA, Ga-DOTA-peptides, Yttrium- and Lutetium-based therapy, and the role of FDG PET. It also covers key information of theranostics.

Autoren/Hrsg.

Fanti, Stefano

Nanni, Cristina

Baum, Richard P.

Baum, Richard

Leseproben

Nuclear Medicine Procedures in the Diagnosis of NET
A Historical Perspective
Anna Margherita Maffione, MDa, Sellam Karunanithi, MDb, Rakesh Kumar, MD, PhDb, Domenico Rubello, MDa*[e-mail] and Abass Alavi, MDc,     aPET Unit, Department of Nuclear Medicine, Santa Maria della Misericordia Hospital, Viale Tre Martiri 140, Rovigo 45100, Italy; bDepartment of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi 110029, India; cDepartment of Radiology, University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA *Corresponding author. Department of Nuclear Medicine, PET/CT Centre, Radiology, Neuroradiology, Medical Physics, Santa Maria della Misericordia Hospital, Viale Tre Martiri, 140, Rovigo 45100, Italy. Novel diagnostic tools and therapies have emerged as a result of the continuous endeavors relating to neuroendocrine tumors (NETs). Nuclear medicine plays a pivotal role in the imaging and treatment of NETs. Somatostatin receptor analogues and metaiodobenzylguanidine remain front-line single-photon emission computed tomography (SPECT) radiotracers in the imaging of NET; their utility has been augmented by the increasing availability of SPECT/CT. Positron emission tomography has been growing rapidly in the imaging of NETs, paralleled by great efforts toward the development of new tracers. Hybrid imaging will play an important role in the future of NETs. Keywords Neuroendocrine tumor Nuclear medicine Imaging Treatment Therapy PET SPECT Key points
• In the last several years, novel diagnostic tools and therapies have emerged as a substantial result of the continuous endeavors relating to neuroendocrine tumors (NETs). • Nuclear medicine plays a pivotal role in the imaging and treatment of NETs. • Somatostatin receptor analogues and metaiodobenzylguanidine remain front-line single-photon emission computed tomography (SPECT) radiotracers in the imaging of NET; their utility has been augmented in recent years by the increasing availability of SPECT/CT. • Positron emission tomography (PET) has been growing rapidly in the imaging of NETs, paralleled by great efforts toward the development of new tracers. • Hybrid imaging, such as PET/CT or PET/magnetic resonance imaging, will play an important role in the future of NETs. Neuroendocrine tumors: a clinical point of view
Pathologic Setting
Originally, the concept of neuroendocrine neoplasm reflected the hypothesis that the cells from which these tumors result from originated from the embryonic neural crest. This concept was invalidated years ago, but the term neuroendocrine tumor (NET) is still recommended by the World Health Organization’s (WHO) most recent edition of the WHO Classification of Tumours of the Digestive System.1 During the last decades, multiple classifications for NET were proposed; as a result, divergences and confusions inevitably emerged, reducing the quality of the reporting data. In the last years, novel diagnostic tools and therapies have emerged as a substantial result of the continuous endeavors on this specific topic. The need for international standards has inexorably arisen. As a consequence, the International Union Against Cancer, the American Joint Cancer Committee, the WHO, and the European Neuroendocrine Tumor Society have attempted to improve the standardization of the classification, grading, and staging of NETs.2–4 Essentially, the new accepted classification consists of 3 main histologic categories: low-grade NETs (grade 1), intermediate-grade NETs (grade 2), and high-grade NETs (grade 3, also called neuroendocrine carcinoma). Grade 1 and 2 are considered well-differentiated tumors (previously defined as either carcinoid or atypical carcinoid), whereas grade 3 is considered poorly differentiated (Table 1).5,6 Table 1 Differentiation and grading of NETs Abbreviation: HPF, high-power field. aMIB1 antibody; percentage of 2000 tumor cells in areas of highest nuclear labeling. b10 HPF = 2 mm2, at least 40 fields (at 40 × magnification) evaluated in areas of highest mitotic density. Differentiation refers to the extent that the neoplastic cells look like their non-neoplastic counterparts; for example, well-differentiated NETs have characteristic organoid architecture, well-differentiated cytology, and produce abundant neurosecretory granules. Grading, conversely, refers to the biologic tumor’s vigor; for example, high-grade tumors are extremely aggressive. The proliferative rate expressed by mitotic count and Ki-67 index (see Table 1) has been repeatedly shown to provide significant prognostic information for NETs7,8; most systems of grading rely extensively on the proliferative rate to separate low-, intermediate-, and high-grade tumors. The new WHO classification, published in 2010,1 has introduced some new considerations about NETs. Firstly, the terms benign and malignant have been eliminated because neuroendocrine neoplasms are all potentially malignant. Therefore, all neuroendocrine neoplasms that were previously regarded as benign have now been considered in the incidence data (for example, Surveillance, Epidemiology, and End Results [SEER] data). Secondly, the term atypical carcinoid is not recommended and it cannot be used for G2 neuroendocrine tumors. Even though endocrine and neuroendocrine are essentially synonymous, the use of neuroendocrine has been once again recommended. The neoplasms composed of both neuroendocrine cells and nonendocrine components (usually adenocarcinoma structures) are classified as mixed adenoneuroendocrine carcinomas (note that neuroendocrine component should exceed at least 30% of all cells). NETs could affect almost every apparatus through the body, but the most common ones arise from the duodenum, ileum, pancreas, bronchus, colon and rectum, stomach, thymus, and heart. A particular subdivision of NETs is represented by functioning and nonfunctioning tumors. Nonfunctioning NETs may not present with clinical symptoms until they produce tumor mass effects at a late stage of growth. Functioning NETs (mostly pancreatic NETs) produce symptoms, sometimes remarkable, because of the excess release of various hormones and biologic amines by the tumor into the blood (histology specific, such as insulin, gastrin, vasoactive intestinal peptide, somatostatin, and glucagons, or generic, like serotonin, prostaglandin, and parathyroid hormone–releasing peptide). Some functioning NETs could result from a background of multiple endocrine neoplasia (MEN); for example, duodenal gastrinoma could be associated with Zollinger-Ellison syndrome within MEN-1, and it is invariably multicentric, different from the sporadic type.9 Epidemiology
The overall incidence rate of NETs has increased since 1975,10,11 although it is uncertain if this tendency is caused by the advent of new diagnostic instrumentations, new NET definitions and classifications, the increased understanding among physicians, or an actual increase in NET incidence. The SEER database analysis shows an impressive 5-fold increase in the diagnosed incidence of NETs from 1973 to 2004,12 and NETs’ incidence is predicted to persist growing at a faster rate than other malignancies.11 NETs are, of course, quite rare, accounting for only 0.5% of all malignancies13; but surprisingly, their prevalence is higher than gastric and pancreatic tumors combined.14 The greater part of NETs occurs in the gastrointestinal tract (about 67%, most of which are in the small intestine) and in the lungs (about 25%).13 NETs of the rectum and appendix usually have a good prognosis, whereas NETs of the colon have the lowest life expectancy (67.4% of 5-year disease-specific survival).10 The prognosis is then obviously associated with the stage: 93% of 5-year survival in local disease, 74% in regional disease, and 19% in metastatic disease.13 Markers
Biochemical NETs markers are substances secreted by the tumor that circulate in the blood and can be used for diagnosis and evaluation. NETs markers can be an expression of nonfunctional NETs, like chromogranin A (CgA), neuron-specific enolase (NSE), 5-Hydroxyindoleacetic acid (5-HIAA), synaptophysin, neurokinin, pancreatic polypeptide, neurotensin, and a and ß human chorionic gonadotropin. Some of these proteins have shown a high accuracy in diagnosing NETs. Currently, CgA is the most accurate marker in diagnosis and for prognosis of NETs and it is suggested to be used for disease monitoring.15 An article by Campana and coworkers16...