|
1
|
Stauff E, Xu W, Kecskemethy HH, Langhans SA, Kandula VVR, Averill LW, Yue X. Tryptophan Kynurenine Pathway-Based Imaging Agents for Brain Disorders and Oncology-From Bench to Bedside. Biomolecules 2025; 15:47. [PMID: 39858441 PMCID: PMC11762981 DOI: 10.3390/biom15010047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Revised: 12/23/2024] [Accepted: 12/28/2024] [Indexed: 01/27/2025] Open
Abstract
Tryptophan (Trp)-based radiotracers have excellent potential for imaging many different types of brain pathology because of their involvement with both the serotonergic and kynurenine (KYN) pathways. However, radiotracers specific to the kynurenine metabolism pathway are limited. In addition, historically Trp-based radiopharmaceuticals were synthesized with the short-lived isotope carbon-11. A newer generation of Trp-based imaging agents using the longer half-lived and commercially available isotopes, such as fluorine-18 and iodine-124, are being developed. The newly developed amino acid-based tracers have been demonstrated to have favorable radiochemical and imaging characteristics in pre-clinical studies. However, many barriers still exist in the clinical translation of KYN pathway-specific radiotracers.
Collapse
Affiliation(s)
- Erik Stauff
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (E.S.); (W.X.); (H.H.K.); (V.V.R.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Wenqi Xu
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (E.S.); (W.X.); (H.H.K.); (V.V.R.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Heidi H. Kecskemethy
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (E.S.); (W.X.); (H.H.K.); (V.V.R.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Sigrid A. Langhans
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
- Division of Neurology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA
| | - Vinay V. R. Kandula
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (E.S.); (W.X.); (H.H.K.); (V.V.R.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Lauren W. Averill
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (E.S.); (W.X.); (H.H.K.); (V.V.R.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
| | - Xuyi Yue
- Department of Radiology, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA; (E.S.); (W.X.); (H.H.K.); (V.V.R.K.); (L.W.A.)
- Diagnostic & Research PET/MR Center, Nemours Children’s Health, Delaware, Wilmington, DE 19803, USA;
- Department of Radiology, Thomas Jefferson University, Philadelphia, PA 19107, USA
| |
Collapse
|
|
2
|
Ramesh A, Chatterjee A, Subramaniam RM. Neuroendocrine Neoplasms: Epidemiology, Diagnosis, and Management. PET Clin 2023; 18:161-168. [PMID: 36707369 DOI: 10.1016/j.cpet.2022.10.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
Abstract
Neuroendocrine tumors have variety of biological and clinical characteristics. The classification of neuroendocrine neoplasm has evolved, and the newest 2019 World Health Organization classification outlines a well-differentiated high-grade G3 subtype, recognizing its differences from the poorly differentiated neuroendocrine carcinoma. 68Ga-DOTAT PET has largely replaced somatostatin scintigraphy as the diagnostic workup choice for NENs. NETest, a multi-analyte liquid biopsy, is a promising recent development in the biochemical diagnosis. Management includes wait and watch approach, surgical resection, somatostatin analogs, 177Lu DOTATATE therapy, chemotherapy, radiotherapy or immunotherapy combinations. Further clinical trials are necessary for determining the appropriate sequencing.
Collapse
Affiliation(s)
- Ajitha Ramesh
- Dunedin Hospital, 201 Great King Street, Dunedin 9016, New Zealand
| | - Aniruddha Chatterjee
- Department of Pathology, Dunedin School of Medicine, University of Otago, PO Box 56, Dunedin 9054, New Zealand
| | - Rathan M Subramaniam
- Department of Medicine, Otago Medical School, University of Otago, 201 Great King Street, Dunedin, New Zealand; Department of Radiology, Duke University, Durham, NC, USA.
| |
Collapse
|
|
3
|
Pellegrino F, Granata V, Fusco R, Grassi F, Tafuto S, Perrucci L, Tralli G, Scaglione M. Diagnostic Management of Gastroenteropancreatic Neuroendocrine Neoplasms: Technique Optimization and Tips and Tricks for Radiologists. Tomography 2023; 9:217-246. [PMID: 36828370 PMCID: PMC9958666 DOI: 10.3390/tomography9010018] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Revised: 01/22/2023] [Accepted: 01/23/2023] [Indexed: 01/31/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) comprise a heterogeneous group of neoplasms, which derive from cells of the diffuse neuroendocrine system that specializes in producing hormones and neuropeptides and arise in most cases sporadically and, to a lesser extent, in the context of complex genetic syndromes. Furthermore, they are primarily nonfunctioning, while, in the case of insulinomas, gastrinomas, glucagonomas, vipomas, and somatostatinomas, they produce hormones responsible for clinical syndromes. The GEP-NEN tumor grade and cell differentiation may result in different clinical behaviors and prognoses, with grade one (G1) and grade two (G2) neuroendocrine tumors showing a more favorable outcome than grade three (G3) NET and neuroendocrine carcinoma. Two critical issues should be considered in the NEN diagnostic workup: first, the need to identify the presence of the tumor, and, second, to define the primary site and evaluate regional and distant metastases. Indeed, the primary site, stage, grade, and function are prognostic factors that the radiologist should evaluate to guide prognosis and management. The correct diagnostic management of the patient includes a combination of morphological and functional evaluations. Concerning morphological evaluations, according to the consensus guidelines of the European Neuroendocrine Tumor Society (ENETS), computed tomography (CT) with a contrast medium is recommended. Contrast-enhanced magnetic resonance imaging (MRI), including diffusion-weighted imaging (DWI), is usually indicated for use to evaluate the liver, pancreas, brain, and bones. Ultrasonography (US) is often helpful in the initial diagnosis of liver metastases, and contrast-enhanced ultrasound (CEUS) can solve problems in characterizing the liver, as this tool can guide the biopsy of liver lesions. In addition, intraoperative ultrasound is an effective tool during surgical procedures. Positron emission tomography (PET-CT) with FDG for nonfunctioning lesions and somatostatin analogs for functional lesions are very useful for identifying and evaluating metabolic receptors. The detection of heterogeneity in somatostatin receptor (SSTR) expression is also crucial for treatment decision making. In this narrative review, we have described the role of morphological and functional imaging tools in the assessment of GEP-NENs according to current major guidelines.
Collapse
Affiliation(s)
| | - Vincenza Granata
- Division of Radiology, Istituto Nazionale Tumori IRCCS Fondazione Pascale—IRCCS di Napoli, 80131 Naples, Italy
| | - Roberta Fusco
- Medical Oncology Division, Igea SpA, 80013 Naples, Italy
| | - Francesca Grassi
- Italian Society of Medical and Interventional Radiology (SIRM), SIRM Foundation, Via della Signora 2, 20122 Milan, Italy
- Division of Radiology, Università degli Studi della Campania Luigi Vanvitelli, 80127 Naples, Italy
| | - Salvatore Tafuto
- S.C. Sarcomi e Tumori Rari, Istituto Nazionale Tumori, IRCCS, Fondazione “G. Pascale”, 80131 Naples, Italy
| | - Luca Perrucci
- Ferrara Department of Interventional and Diagnostic Radiology, Ospedale di Lagosanto, Azienda AUSL, 44023 Ferrara, Italy
| | - Giulia Tralli
- Department of Radiology, Ospedale Santa Maria della Misericordia, 45100 Rovigo, Italy
| | - Mariano Scaglione
- Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy
| |
Collapse
|
|
4
|
Shegani A, Kealey S, Luzi F, Basagni F, Machado JDM, Ekici SD, Ferocino A, Gee AD, Bongarzone S. Radiosynthesis, Preclinical, and Clinical Positron Emission Tomography Studies of Carbon-11 Labeled Endogenous and Natural Exogenous Compounds. Chem Rev 2023; 123:105-229. [PMID: 36399832 PMCID: PMC9837829 DOI: 10.1021/acs.chemrev.2c00398] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Indexed: 11/19/2022]
Abstract
The presence of positron emission tomography (PET) centers at most major hospitals worldwide, along with the improvement of PET scanner sensitivity and the introduction of total body PET systems, has increased the interest in the PET tracer development using the short-lived radionuclides carbon-11. In the last few decades, methodological improvements and fully automated modules have allowed the development of carbon-11 tracers for clinical use. Radiolabeling natural compounds with carbon-11 by substituting one of the backbone carbons with the radionuclide has provided important information on the biochemistry of the authentic compounds and increased the understanding of their in vivo behavior in healthy and diseased states. The number of endogenous and natural compounds essential for human life is staggering, ranging from simple alcohols to vitamins and peptides. This review collates all the carbon-11 radiolabeled endogenous and natural exogenous compounds synthesised to date, including essential information on their radiochemistry methodologies and preclinical and clinical studies in healthy subjects.
Collapse
Affiliation(s)
- Antonio Shegani
- School
of Biomedical Engineering & Imaging Sciences, King’s College London, King’s Health Partners, St Thomas’ Hospital, London SE1 7EH, United Kingdom
| | - Steven Kealey
- School
of Biomedical Engineering & Imaging Sciences, King’s College London, King’s Health Partners, St Thomas’ Hospital, London SE1 7EH, United Kingdom
| | - Federico Luzi
- School
of Biomedical Engineering & Imaging Sciences, King’s College London, King’s Health Partners, St Thomas’ Hospital, London SE1 7EH, United Kingdom
| | - Filippo Basagni
- Department
of Pharmacy and Biotechnology, Alma Mater
Studiorum−University of Bologna, via Belmeloro 6, 40126 Bologna, Italy
| | - Joana do Mar Machado
- School
of Biomedical Engineering & Imaging Sciences, King’s College London, King’s Health Partners, St Thomas’ Hospital, London SE1 7EH, United Kingdom
| | - Sevban Doğan Ekici
- School
of Biomedical Engineering & Imaging Sciences, King’s College London, King’s Health Partners, St Thomas’ Hospital, London SE1 7EH, United Kingdom
| | - Alessandra Ferocino
- Institute
of Organic Synthesis and Photoreactivity, Italian National Research Council, via Piero Gobetti 101, 40129 Bologna, Italy
| | - Antony D. Gee
- School
of Biomedical Engineering & Imaging Sciences, King’s College London, King’s Health Partners, St Thomas’ Hospital, London SE1 7EH, United Kingdom
| | - Salvatore Bongarzone
- School
of Biomedical Engineering & Imaging Sciences, King’s College London, King’s Health Partners, St Thomas’ Hospital, London SE1 7EH, United Kingdom
| |
Collapse
|
|
5
|
Cross-Sectional Imaging Findings of Atypical Liver Malignancies and Diagnostic Pitfalls. Radiol Clin North Am 2022; 60:775-794. [DOI: 10.1016/j.rcl.2022.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
|
|
6
|
Bodei L, Jayaprakasam VS, Kidd M, Gilardi L, Volterrani D, Paganelli G, Grana CM, Modlin IM. Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors. NUCLEAR ONCOLOGY 2022:933-974. [DOI: 10.1007/978-3-031-05494-5_18] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
7
|
Tabacchi E, Nanni C, Bossert I, Maffione AM, Fanti S. Diagnostic Applications of Nuclear Medicine: Pancreatic Cancer. NUCLEAR ONCOLOGY 2022:891-917. [DOI: 10.1007/978-3-031-05494-5_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
8
|
Sakharuk I, Harner A, McKenzie J, Arfa A, Ullah A, Belakhlef S, Kruse J. Large Primary Neuroendocrine Tumor of the Liver in a 57-year-Old Female Presenting With MSSA Bacteremia. Am Surg 2021; 88:778-780. [PMID: 34734552 DOI: 10.1177/00031348211050825] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
Primary neuroendocrine tumors (NETs) are rare forms of malignancy, representing just .5% of known cancers and having an overall incidence of 0.2/100,000. The most common sites of origin are bronchopulmonary and gastrointestinal, most commonly the appendix, pancreas, and ileum. We report the case of a 57-year-old female who was admitted for refractory MSSA bacteremia and several weeks of abdominal pain. CT imaging done on presentation demonstrated a 12.5 x 19.4 x 17.3 cm heterogeneous right liver mass with associated mass effect. The patient was taken to the operating room and a right hepatectomy and cholecystectomy were performed without complication. Histological examination revealed necrotic tumor in sheets and nests with marked nuclear pleomorphism. Immunohistochemistry demonstrated positive staining for pancytokeratin, synaptophysin, chromogranin, and TTF-1, consistent with undifferentiated NET. While rare, NETs can originate from a variety of organs outside the gastrointestinal and bronchopulmonary tract, including the liver.
Collapse
Affiliation(s)
- Ilya Sakharuk
- Department of Surgery, 160343Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - Andrew Harner
- Department of Surgery, 160343Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - Janie McKenzie
- Department of Surgery, 160343Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - Ahmed Arfa
- Department of Pathology, 160343Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - Asad Ullah
- Department of Pathology, 160343Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - Sami Belakhlef
- Department of Pathology, 160343Medical College of Georgia at Augusta University, Augusta, GA, USA
| | - J Kruse
- Department of Surgery, 160343Medical College of Georgia at Augusta University, Augusta, GA, USA
| |
Collapse
|
|
9
|
Zhang Z, Zhao X, Li Z, Wu Y, Liu Y, Li Z, Li G. Development of a nomogram model to predict survival outcomes in patients with primary hepatic neuroendocrine tumors based on SEER database. BMC Cancer 2021; 21:567. [PMID: 34006241 PMCID: PMC8130428 DOI: 10.1186/s12885-021-08337-y] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Accepted: 03/30/2021] [Indexed: 12/15/2022] Open
Abstract
Background Primary hepatic neuroendocrine tumors (PH-NETs) are extremely rare and unknown. Because of its rarity, its prognosis features and influencing factors are not well established. Methods Data of 140 patients with PH-NETs diagnosed in the SEER database from 1975 to 2016 were collected. The demographics and clinic-pathological features were described. By using propensity-score matching (PSM) analysis, three associated cohorts were selected to describe the malignancy of PH-NETs and univariate analysis was conducted. Then, multivariate Cox analyses were performed and a predicting nomograph was constructed. C-index, receiver operating characteristic (ROC) curve and calibration curves were used to evaluate the predictive value of nomogram. Results The overall survival outcomes of PH-NETs were superior to hepatocellular carcinoma (HCC) with a mean survival time 30.64 vs 25.11 months (p = 0.052), but inferior to gastrointestinal tract neuroendocrine tumors in situ (GI-NETs in situ) with a mean survival time 30.64 vs 41.62 months (p = 0.017). With reference to gastrointestinal neuroendocrine tumors with liver metastasis (GI-NETs-LM), GI-NETs-LM had better outcomes in short time (1-year survival rate: 64.75% vs 56.43%) but was worse in long time (5-year survival rate: 8. 63% vs 18.57%). Multivariate Cox analyses showed that tumor grade and surgery were two independent factors for prognosis of the patients (p < 0.00). Tumor grade and surgery were used to construct the predicting nomogram. The C-index was 0.79 (95%CI = 0.75–0.83). The area under curve (AUC) values in ROC were 0.868 in 1-year and 0.917 in 3-year survival and the calibration curves showed good consistency. Conclusions The overall prognosis PH-NETs is generally favorable, better than HCC and GI-NETs-LM in long term. Preoperative biopsy and complete pathological diagnosis were recommended. Radical surgical intervention including transplantation was the first choice in PH-NETs therapy. Supplementary Information The online version contains supplementary material available at 10.1186/s12885-021-08337-y.
Collapse
Affiliation(s)
- Ziteng Zhang
- Department of Hepato-Biliary Surgery, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China
| | - Xin Zhao
- Department of Hepato-Biliary Surgery, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China
| | - Zhiyan Li
- Department of Ultrasonography, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China
| | - Youchun Wu
- Department of Hepato-Biliary Surgery, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China
| | - Yao Liu
- Department of Hepatology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, China
| | - Zhiwei Li
- Department of Hepato-Biliary Surgery, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China.
| | - Guobao Li
- Department of Lung Disease, Shenzhen Third People's Hospital, The Second Affiliated Hospital, Southern University of Science and Technology, Shenzhen, 518055, China.
| |
Collapse
|
|
10
|
Jawlakh H, Velikyan I, Welin S, Sundin A. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI are superior to 68 Ga-DOTATOC-PET/CT for neuroendocrine tumour imaging. J Neuroendocrinol 2021; 33:e12981. [PMID: 34046974 DOI: 10.1111/jne.12981] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Revised: 04/07/2021] [Accepted: 04/26/2021] [Indexed: 12/13/2022]
Abstract
The present study aimed to assess gadoxetate disodium contrast-enhanced (CE) positron emission tomography (PET)/magnetic resonance imaging (MRI) with 68 Ga-DOTATOC and 11 C-5-Hydroxy-tryptophan (11 C-5-HTP) in comparison with iodine CE 68 Ga-DOTATOC-PET/computed tomography (CT) for neuroendocrine tumour imaging. Detection rate and reader's confidence were evaluated for each separate image volume: CE-CT, CE-MRI including diffusion-weighted imaging, 68 Ga-DOTATOC-PET performed at PET/CT, 68 Ga-DOTATOC-PET performed at PET/MRI and 11 C-5-HTP-PET, and for the three combined hybrid examinations 68 Ga-DOTATOC-PET/MRI, 11 C-5-HTP-PET/MRI and 68 Ga-DOTATOC-PET/CT. In 11 patients, 255 lesions were depicted. 68 Ga-DOTATOC-PET performed at PET/MRI depicted 72.5%, 68 Ga-DOTATOC-PET performed at PET/CT depicted 62.7%, 11 C-5-HTP-PET depicted 68.2% and CE-CT depicted 53% of lesions. 68 Ga-DOTATOC-PET performed at PET/MRI (P < 0.001) and PET/CT (P = 0.02), 11 C-5-HTP-PET (P < 0.001) and MRI (P < 0.001) were superior to CT. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI detected 92.5% and 92% of lesions, respectively, and both outperformed 68 Ga-DOTATOC-PET/CT (65%) (P < 0.001). For liver metastasis imaging, MRI alone was unsurpassed (P < 0.01) and 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI outperformed 68 Ga-DOTATOC-PET/CT (P < 0.001). For lymph node metastasis diagnosis, 68 Ga-DOTATOC-PET performed at PET/MRI and PET/CT and 11 C-5-HTP-PET detected 94%, 94% and 94% of lesions, respectively, and outperformed MRI and CE-CT alone (P < 0.001). For bone metastasis imaging, 68 Ga-DOTATOC-PET performed at PET/MRI and PET/CT and 11 C-5-HTP-PET performed equally well (P = 0.05) and better than MRI. Reader's confidence was better for 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI than for 68 Ga-DOTATOC-PET/CT. The tumour maximum standardised uptake value and tumour-to-liver ratio were both approximately twice as high as for 68 Ga-DOTATOC than for 11 C-5-HTP. 68 Ga-DOTATOC-PET/MRI and 11 C-5-HTP-PET/MRI provided the highest detection rates and reader's confidence and were both superior to 68 Ga-DOTATOC-PET/CT, mainly because of the MRI component. The imaging contrast with 68 Ga-DOTATOC was superior to that of 11 C-5-HTP.
Collapse
Affiliation(s)
- Hiba Jawlakh
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Irina Velikyan
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
| | - Staffan Welin
- Department of Medical Sciences, Uppsala University, Uppsala, Sweden
| | - Anders Sundin
- Department of Surgical Sciences, Radiology and Molecular Imaging, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
11
|
Park A, Martin A, Carlos R, Neychev V. Primary versus secondary nature of mesenteric neuroendocrine tumours. BMJ Case Rep 2021; 14:14/2/e239217. [PMID: 33541996 PMCID: PMC7868254 DOI: 10.1136/bcr-2020-239217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumours (NETs) are rare group of malignancy that originate from neuroendocrine cells present throughout the body. Most patients with NET first present with symptoms associated with metastasis, and up to 20% of patients have unknown primary site of tumour. Most common metastatic sites for small intestine NETs (SI-NETs) are the locoregional lymph nodes and liver. Although mesenteric metastasis through direct extension or lymphatic spread from SI-NETs is common, mesenteric extranodal involvement is extremely rare, and its biology and primary versus secondary nature are not well understood. Due to their small size and location, SI-NETs are frequently undetected on anatomical imaging or indium-111-pentetreotide single-photon emission computed tomography/CT (Octreoscan) and are difficult to be found via endoscopy. Gallium-68-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-octreotate positron emission tomography (68Ga-DOTATATE PET)/CT has been increasingly used for accurate staging, unknown primary tumour site localisation and appropriate management planning. We present a case of an incidentally found mesenteric NET with occult SI-NETs localised preoperatively by 68Ga-DOTATATE PET/CT.
Collapse
Affiliation(s)
- Ariel Park
- University of Central Florida College of Medicine, Orlando, Florida, USA
| | - Alicia Martin
- University of Central Florida College of Medicine, Orlando, Florida, USA
| | - Ramos Carlos
- Department of Pathology, Central Florida Regional Hospital, Sanford, Florida, USA
| | - Vladimir Neychev
- Department of Clinical Sciences, University of Central Florida College of Medicine, Orlando, Florida, USA
| |
Collapse
|
|
12
|
Goud NS, Bhattacharya A, Joshi RK, Nagaraj C, Bharath RD, Kumar P. Carbon-11: Radiochemistry and Target-Based PET Molecular Imaging Applications in Oncology, Cardiology, and Neurology. J Med Chem 2021; 64:1223-1259. [PMID: 33499603 DOI: 10.1021/acs.jmedchem.0c01053] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
The positron emission tomography (PET) molecular imaging technique has gained its universal value as a remarkable tool for medical diagnosis and biomedical research. Carbon-11 is one of the promising radiotracers that can report target-specific information related to its pharmacology and physiology to understand the disease status. Currently, many of the available carbon-11 (t1/2 = 20.4 min) PET radiotracers are heterocyclic derivatives that have been synthesized using carbon-11 inserted different functional groups obtained from primary and secondary carbon-11 precursors. A spectrum of carbon-11 PET radiotracers has been developed against many of the upregulated and emerging targets for the diagnosis, prognosis, prediction, and therapy in the fields of oncology, cardiology, and neurology. This review focuses on the carbon-11 radiochemistry and various target-specific PET molecular imaging agents used in tumor, heart, brain, and neuroinflammatory disease imaging along with its associated pathology.
Collapse
Affiliation(s)
- Nerella Sridhar Goud
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Ahana Bhattacharya
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Raman Kumar Joshi
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Chandana Nagaraj
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Rose Dawn Bharath
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| | - Pardeep Kumar
- Department of Neuroimaging and Interventional Radiology (NIIR), National Institute of Mental Health and Neuro Sciences (NIMHANS), Bengaluru 560 029, India
| |
Collapse
|
|
13
|
Joosten L, Boss M, Jansen T, Brom M, Buitinga M, Aarntzen E, Eriksson O, Johansson L, de Galan B, Gotthardt M. Molecular Imaging of Diabetes. Mol Imaging 2021. [DOI: 10.1016/b978-0-12-816386-3.00041-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022] Open
|
|
14
|
Eriksson O, Långström B, Antoni G. News ways of understanding the complex biology of diabetes using PET. Nucl Med Biol 2021; 92:65-71. [PMID: 32387114 DOI: 10.1016/j.nucmedbio.2020.04.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 03/27/2020] [Accepted: 04/15/2020] [Indexed: 11/22/2022]
Abstract
The understanding of metabolic disease and diabetes on a molecular level has increased significantly due to the recent advances in molecular biology and biotechnology. However, in vitro studies and animal models do not always translate to the human disease, perhaps illustrated by the failure of many drug candidates in the clinical phase. Non-invasive biomedical imaging techniques such as Positron Emission Tomography (PET) offer tools for direct visualization and quantification of molecular processes in humans. Developments in this area potentially enable longitudinal in vivo studies of receptors and processes involved in diabetes guiding drug development and diagnosis in the near future. This mini-review focuses on describing the overall perspective of how PET can be used to increase our understanding and improve treatment of diabetes. The methodological aspects and future developments and challenges are highlighted.
Collapse
Affiliation(s)
- O Eriksson
- Science for Life Laboratory, Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden; Antaros Medical AB, Mölndal, Sweden
| | - B Långström
- Department of Chemistry, Uppsala University, Uppsala, Sweden
| | - G Antoni
- Department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
| |
Collapse
|
|
15
|
Zlatopolskiy BD, Endepols H, Krasikova RN, Fedorova OS, Ermert J, Neumaier B. 11C- and 18F-labelled tryptophans as PET-tracers for imaging of altered tryptophan metabolism in age-associated disorders. RUSSIAN CHEMICAL REVIEWS 2020. [DOI: 10.1070/rcr4954] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
The ageing of the world’s population is the result of increased life expectancy observed in almost all countries throughout the world. Consequently, a rising tide of ageing-associated disorders, like cancer and neurodegenerative diseases, represents one of the main global challenges of the 21st century. The ability of mankind to overcome these challenges is directly dependent on the capability to develop novel methods for therapy and diagnosis of age-associated diseases. One hallmark of age-related pathologies is an altered tryptophan metabolism. Numerous pathological processes including neurodegenerative and neurological diseases like epilepsy, Parkinson’s and Alzheimer’s diseases, cancer and diabetes exhibit marked changes in tryptophan metabolism. Visualization of key processes of tryptophan metabolic pathways, especially using positron emission tomography (PET) and related hybrid methods like PET/CT and PET/MRI, can be exploited to early detect the aforementioned disorders with considerable accuracy, allowing appropriate and timely treatment of patients. Here we review the published 11C- and 18F-labelled tryptophans with respect to the production and also preclinical and clinical evaluation as PET-tracers for visualization of different branches of tryptophan metabolism.
The bibliography includes 159 references.
Collapse
|
|
16
|
Giammarile F, Castellucci P, Dierckx R, Estrada Lobato E, Farsad M, Hustinx R, Jalilian A, Pellet O, Rossi S, Paez D. Non-FDG PET/CT in Diagnostic Oncology: a pictorial review. Eur J Hybrid Imaging 2019; 3:20. [PMID: 34191163 PMCID: PMC8218094 DOI: 10.1186/s41824-019-0066-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Accepted: 10/22/2019] [Indexed: 11/25/2022] Open
Abstract
Positron emission tomography/computed tomography (PET/CT) is currently one of the main imaging modalities for cancer patients worldwide. Fluorodeoxyglucose (FDG) PET/CT has earned its global recognition in the modern management of cancer patients and is rapidly becoming an important imaging modality for patients with cardiac, neurological, and infectious/inflammatory conditions. Despite its proven benefits, FDG has limitations in the assessment of several relevant tumours such as prostate cancer. Therefore, there has been a pressing need for the development and clinical application of different PET radiopharmaceuticals that could image these tumours more precisely. Accordingly, several non-FDG PET radiopharmaceuticals have been introduced into the clinical arena for management of cancer. This trend will undoubtedly continue to spread internationally. The use of PET/CT with different PET radiopharmaceuticals specific to tumour type and biological process being assessed is part of the personalised precision medicine approach. The objective of this publication is to provide a case-based method of understanding normal biodistribution, variants, and pitfalls, including several examples of different imaging appearances for the main oncological indications for each of the new non-FDG PET radiopharmaceuticals. This should facilitate the interpretation and recognition of common variants and pitfalls to ensure that, in clinical practice, the official report is accurate and helpful. Some of these radiopharmaceuticals are already commercially available in many countries (e.g. 68Ga-DOTATATE and DOTATOC), others are in the process of becoming available (e.g. 68Ga-PSMA), and some are still being researched. However, this list is subject to change as some radiopharmaceuticals are increasingly utilised, while others gradually decrease in use.
Collapse
Affiliation(s)
- Francesco Giammarile
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria.
| | - Paolo Castellucci
- Department of Nuclear Medicine, Sant'Orsola-Malpighi Hospital, 40138, Bologna, Italy
| | - Rudi Dierckx
- Medical Imaging Center, Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, The Netherlands
| | - Enrique Estrada Lobato
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| | - Mohsen Farsad
- Department of Nuclear Medicine, Bolzano Hospital, Bolzano, Italy
| | - Roland Hustinx
- Department of Nuclear Medicine, CHU Liège, University of Liège, Liège, Belgium
| | - Amirreza Jalilian
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| | - Olivier Pellet
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| | - Susana Rossi
- Centro Uruguayo de Imagenología Molecular (CUDIM), Montevideo, Uruguay
| | - Diana Paez
- Department of Nuclear Sciences and Applications, International Atomic Energy Agency, Vienna, Austria
| |
Collapse
|
|
17
|
Kim HY, Lee JY, Lee YS, Jeong JM. Design and synthesis of enantiopure 18 F-labelled [ 18 F]trifluoromethyltryptophan from 2-halotryptophan derivatives via copper(I)-mediated [ 18 F]trifluoromethylation and evaluation of its in vitro characterization for the serotonergic system imaging. J Labelled Comp Radiopharm 2019; 62:566-579. [PMID: 31134670 DOI: 10.1002/jlcr.3772] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 05/15/2019] [Accepted: 05/20/2019] [Indexed: 11/06/2022]
Abstract
We synthesized [18 F]trifluoromethyl-l-tryptophan ([18 F]CF3 -l-Trp) using Cu(I)-mediated [18 F]trifluoromethylation to image serotonergic system. Radiochemical yield was 6 ± 1.5% (n = 9), and radiochemical purity was over 99%. The molar activity was 0.44 to 0.76 GBq/μmol. [18 F]CF3 -l-Trp was stable for up to 6 hours in mouse and human sera at 37°C. Protein-binding was 0.26 ± 0.03% and 0.34 ± 0.02% in human and mouse serum at 60 minutes, respectively. In conclusion, enantiopure [18 F]CF3 -l-Trp was synthesized as a feasible imaging agent for the serotonergic system.
Collapse
Affiliation(s)
- Ho Young Kim
- Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ji Youn Lee
- Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea
| | - Yun-Sang Lee
- Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae Min Jeong
- Department of Nuclear Medicine, Institute of Radiation Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.,Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Republic of Korea.,Cancer Research Institute, Seoul National University College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
18
|
Wei W, Ehlerding EB, Lan X, Luo QY, Cai W. Molecular imaging of β-cells: diabetes and beyond. Adv Drug Deliv Rev 2019; 139:16-31. [PMID: 31378283 DOI: 10.1016/j.addr.2018.06.022] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2017] [Revised: 04/27/2018] [Accepted: 06/26/2018] [Indexed: 02/09/2023]
Abstract
Since diabetes is becoming a global epidemic, there is a great need to develop early β-cell specific diagnostic techniques for this disorder. There are two types of diabetes (i.e., type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM)). In T1DM, the destruction of pancreatic β-cells leads to reduced insulin production or even absolute insulin deficiency, which consequently results in hyperglycemia. Actually, a central issue in the pathophysiology of all types of diabetes is the relative reduction of β-cell mass (BCM) and/or impairment of the function of individual β-cells. In the past two decades, scientists have been trying to develop imaging techniques for noninvasive measurement of the viability and mass of pancreatic β-cells. Despite intense scientific efforts, only two tracers for positron emission tomography (PET) and one contrast agent for magnetic resonance (MR) imaging are currently under clinical evaluation. β-cell specific imaging probes may also allow us to precisely and specifically visualize transplanted β-cells and to improve transplantation outcomes, as transplantation of pancreatic islets has shown promise in treating T1DM. In addition, some of these probes can be applied to the preoperative detection of hidden insulinomas as well. In the present review, we primarily summarize potential tracers under development for imaging β-cells with a focus on tracers for PET, SPECT, MRI, and optical imaging. We will discuss the advantages and limitations of the various imaging probes and extend an outlook on future developments in the field.
Collapse
|
|
19
|
Abstract
Neuroendocrine tumours (NETs) are neoplasms that arise from neuroendocrine cells. Neuroendocrine cells and their tumours can secrete a wide range of amines and polypeptide hormones into the systemic circulation. This feature has triggered widespread investigation into circulating biomarkers for the diagnosis of NETs as well as for the prediction of the biological behaviour of tumour cells. Classic examples of circulating biomarkers for gastroenteropancreatic NETs include chromogranin A, neuron-specific enolase and pancreatic polypeptide as well as hormones that elicit clinical syndromes, such as serotonin and its metabolites, insulin, glucagon and gastrin. Biomarker metrics of general markers for diagnosing all gastroenteropancreatic NET subtypes are limited, but specific hormonal measurements can be of diagnostic value in select cases. In the past decade, methods for detecting circulating transcripts and tumour cells have been developed to improve the diagnosis of patients with NETs. Concurrently, modern scanning techniques and superior radiotracers for functional imaging have markedly expanded the options for clinicians dealing with NETs. Here, we review the latest research on biomarkers in the NET field to provide clinicians with a comprehensive overview of relevant diagnostic biomarkers that can be implemented in dedicated situations.
Collapse
Affiliation(s)
- Johannes Hofland
- ENETS Center of Excellence, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands.
| | - Wouter T Zandee
- ENETS Center of Excellence, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands
| | - Wouter W de Herder
- ENETS Center of Excellence, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, Netherlands
| |
Collapse
|
|
20
|
Abstract
Somatostatin receptor imaging constitutes an integral part in neuroendocrine tumor visualization and should, because of its vastly superior performance, use 68Ga-DOTA-somatostatin analogue-PET/computed tomography rather than scintigraphy; it is particularly valuable for detecting metastases to lymph nodes, bone, peritoneum, and liver, which may be missed by morphologic imaging. 18FDG-PET/computed tomography is better suited for G3 and high-G2 neuroendocrine tumors. 18FDG-PET/computed tomography provides prognostic information. Alternative available PET tracers are 18F-DOPA and 11C-5-hydroxytryptophan. To take full advantage of the technique PET/computed tomography should include diagnostic intravenous contrast-enhanced computed tomography. PET/MRI is currently mainly investigational.
Collapse
Affiliation(s)
- Anders Sundin
- Department of Radiology, Molecular Imaging, Institution of Surgical Sciences, Uppsala University, Uppsala University Hospital, Uppsala SE-751 85, Sweden.
| |
Collapse
|
|
21
|
Abstract
Neuroendocrine tumors, including carcinoids, are rare and insidiously growing tumors. Related to their site of origin, tumors can be functional, causing various forms of the carcinoid syndrome, owing to the overproduction of serotonin, histamine, or other bioactive substances. They often invade adjacent structures or metastasize to the liver and elsewhere. Treatment includes multimodal approaches, including cytoreductive surgery, locoregional embolization, cytotoxic therapy, peptide receptor radionuclide therapy, and various targeted therapies with goals of symptom relief and control of tumor growth. This article summarizes current and emerging approaches to management and reviews several promising future therapies.
Collapse
Affiliation(s)
- Paul Benjamin Loughrey
- Department of Ophthalmology, Royal Victoria Hospital, Belfast Trust, Grosvenor Road, Belfast, BT12 6BA, UK; Department of Endocrinology and Diabetes, Royal Victoria Hospital, Belfast Trust, Grosvenor Road, Belfast, BT12 6BA, UK
| | - Dongyun Zhang
- Department of Medicine, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA
| | - Anthony P Heaney
- Department of Medicine, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA; Department of Neurosurgery, David Geffen School of Medicine, University of California, 700 Tiverton Avenue, Los Angeles, CA 90095, USA.
| |
Collapse
|
|
22
|
Abstract
The concept of neuroendocrine tumors (NETs) began in the 1900s with Oberndorfer's description of carcinoid tumors, followed by specific cytotoxic agents and the identification of somatostatin. NETs diagnosis was confirmed by World Health Organization classification. Histopathology included immunohistochemistry with specific antibodies. Imaging was refined with molecular imaging. Somatostatin is the leading agent for controlling clinical symptoms related to hormone production. Increasing interest in these tumors, previously thought rare, led to increased incidence and prevalence. Between 1960 and 1970, the true NET-concept was established with development of radioimmunoassays for peptides and hormones, and imaging with computerized tomography.
Collapse
Affiliation(s)
- Kjell Öberg
- Department of Endocrine Oncology, Uppsala University Hospital, Entrance 40:5, SE-75185, Uppsala, Sweden.
| |
Collapse
|
|
23
|
Lee L, Ito T, Jensen RT. Imaging of pancreatic neuroendocrine tumors: recent advances, current status, and controversies. Expert Rev Anticancer Ther 2018; 18:837-860. [PMID: 29973077 PMCID: PMC6283410 DOI: 10.1080/14737140.2018.1496822] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Recently, there have been a number of advances in imaging pancreatic neuroendocrine tumors (panNETs), as well as other neuroendocrine tumors (NETs), which have had a profound effect on the management and treatment of these patients, but in some cases are also associated with controversies. Areas covered: These advances are the result of numerous studies attempting to better define the roles of both cross-sectional imaging, endoscopic ultrasound, with or without fine-needle aspiration, and molecular imaging in both sporadic and inherited panNET syndromes; the increased attempt to develop imaging parameters that correlate with tumor classification or have prognostic value; the rapidly increasing use of molecular imaging in these tumors and the attempt to develop imaging parameters that correlate with treatment/outcome results. Each of these areas and the associated controversies are reviewed. Expert commentary: There have been numerous advances in all aspects of the imaging of panNETs, as well as other NETs, in the last few years. The advances are leading to expanded roles of imaging in the management of these patients and the results being seen in panNETs/GI-NETs with these newer techniques are already being used in more common tumors.
Collapse
Affiliation(s)
- Lingaku Lee
- a Department of Medicine and Bioregulatory Science , Graduate School of Medical Sciences, Kyushu University , Fukuoka , Japan
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
| | - Tetsuhide Ito
- c Neuroendocrine Tumor Centra, Fukuoka Sanno Hospital International University of Health and Welfare 3-6-45 Momochihama , Sawara-Ku, Fukuoka , Japan
| | - Robert T Jensen
- b Digestive Diseases Branch , NIDDK, NIH , Bethesda , MD , USA
| |
Collapse
|
|
24
|
Yu R, Wachsman A. Imaging of Neuroendocrine Tumors: Indications, Interpretations, Limits, and Pitfalls. Endocrinol Metab Clin North Am 2017; 46:795-814. [PMID: 28760239 DOI: 10.1016/j.ecl.2017.04.008] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Imaging is critical in the diagnosis, prognosis, and management of neuroendocrine tumors (NETs). NETs share common imaging features, but each type exhibits unique features. Computed tomography scans or MRI of the abdomen is used to assess tumor burden routinely. Functional imaging with octreotide scan or gallium-68 somatostatin analog PET is used selectively to confirm diagnosis and guide therapy. Clinicians and radiologists should be familiar with the indications and interpretations of imaging modalities. Novel functional imaging modalities likely will be developed to detect small NETs, predict prognosis, guide therapeutic choices, and design novel therapies.
Collapse
Affiliation(s)
- Run Yu
- Division of Endocrinology, Diabetes & Metabolism, UCLA David Geffen School of Medicine, 200 Medical Plaza Driveway #530, Los Angeles, CA 90095, USA.
| | - Ashley Wachsman
- Department of Imaging, Cedars-Sinai Medical Center, 8700 Beverly Boulevard #M335, Los Angeles, CA 90048, USA
| |
Collapse
|
|
25
|
Abstract
Cushing syndrome (CS) is caused by chronic exposure to excess glucocorticoids. Early recognition and treatment of hypercortisolemia can lead to decreased morbidity and mortality. The diagnosis of CS and thereafter, establishing the cause can often be difficult, especially in patients with mild and cyclic hypercortisolism. Surgical excision of the cause of excess glucocorticoids is the optimal treatment for CS. Medical therapy (steroidogenesis inhibitors, medications that decrease adrenocorticotropic hormone [ACTH] levels or glucocorticoid antagonists) and pituitary radiotherapy may be needed as adjunctive treatment modalities in patients with residual, recurrent or metastatic disease, in preparation for surgery, or when surgery is contraindicated. A multidisciplinary team approach, individualized treatment plan and long-term follow-up are important for optimal management of hypercortisolemia and the comorbidities associated with CS. ABBREVIATIONS ACTH = adrenocorticotropic hormone; BIPSS = bilateral inferior petrosal sinus sampling; CBG = corticosteroid-binding globulin; CD = Cushing disease; CRH = corticotropin-releasing hormone; CS = Cushing syndrome; Dex = dexamethasone; DST = dexamethasone suppression test; EAS = ectopic ACTH syndrome; FDA = U.S. Food & Drug Administration; HDDST = high-dose DST; IPS/P = inferior petrosal sinus to peripheral; MRI = magnetic resonance imaging; NET = neuroendocrine tumor; PET = positron emission tomography; UFC = urinary free cortisol.
Collapse
|
|
26
|
Yang K, Cheng YS, Yang JJ, Jiang X, Guo JX. Primary hepatic neuroendocrine tumors: multi-modal imaging features with pathological correlations. Cancer Imaging 2017; 17:20. [PMID: 28683830 PMCID: PMC5501439 DOI: 10.1186/s40644-017-0120-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2017] [Accepted: 06/16/2017] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Primary hepatic neuroendocrine carcinomas (PHNECs) are rare and asymptomatic, and are therefore difficult to distinguish radiologically from other liver carcinomas. In this study, we aimed to determine the computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA) features of PHNECs. METHODS A retrospective analysis of 11 patients with pathologically proven PHNECs was performed from January 2009 to September 2014. The CT, MRI, and DSA image features were analysed. RESULTS Ten of the eleven patients exhibited two or more lesions, and one patient exhibited a single lesion. Abdominal CT of 8 cases revealed multiple round or oval-shaped masses with well-defined borders, which were heterogeneous and hypodense on precontrast CT images. Significant diffuse heterogeneous enhancement was observed during the arterial phase in 8 cases, and the enhancement was slightly higher than the attenuation of the surrounding normal liver parenchyma and indistinct edges of small lesions during the portal phase. Well circumscribed (11 cases), lobulated (5 cases) or multiple nodular masses (4 cases), nodule (1 case) and irregular masses (1 case) of high signal intensity were observed on T2WI and DWI of MR images. The masses were well circumscribed, heterogeneous, and hypointense on T1WI, with significant enhancement of the solid carcinoma portion in the early arterial phase and continued enhancement in the portal venous phase. Characteristic lobulated or multiple nodular masses were observed in MRI. DSA showed multiple hypervascular carcinoma-staining lesions with sharp edges in the arterial phase. CONCLUSION The CT, MRI, and DSA images of PHNECs exhibit specific characteristic features. Appropriate combinations of the available imaging modalities could therefore optimize the evaluation of patients with PHNECs.
Collapse
Affiliation(s)
- Kai Yang
- Department of Radiology and Medical Imaging, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, 600 Yi Shan Road, Shanghai, 200233 China
| | - Ying-Sheng Cheng
- Department of Radiology and Medical Imaging, Shanghai Sixth People’s Hospital, Shanghai Jiao Tong University, 600 Yi Shan Road, Shanghai, 200233 China
| | - Ji-Jin Yang
- Department of Interventional Radiology, Affiliated Changhai Hospital of Second Military Medical University, Shanghai, 200433 China
| | - Xu Jiang
- Department of Interventional Radiology, Affiliated Changhai Hospital of Second Military Medical University, Shanghai, 200433 China
| | - Ji-Xiang Guo
- Department of Interventional Radiology, Affiliated Changhai Hospital of Second Military Medical University, Shanghai, 200433 China
| |
Collapse
|
|
27
|
Carlbom L, Caballero-Corbalán J, Granberg D, Sörensen J, Eriksson B, Ahlström H. Whole-body MRI including diffusion-weighted MRI compared with 5-HTP PET/CT in the detection of neuroendocrine tumors. Ups J Med Sci 2017; 122:43-50. [PMID: 27894208 PMCID: PMC5361431 DOI: 10.1080/03009734.2016.1248803] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
AIM We wanted to explore if whole-body magnetic resonance imaging (MRI) including diffusion-weighted (DW) and liver-specific contrast agent-enhanced imaging could be valuable in lesion detection of neuroendocrine tumors (NET). [11C]-5-Hydroxytryptophan positron emission tomography/computed tomography (5-HTP PET/CT) was used for comparison. MATERIALS AND METHODS Twenty-one patients with NET were investigated with whole-body MRI, including DW imaging (DWI) and contrast-enhanced imaging of the liver, and whole-body 5-HTP PET/CT. Seven additional patients underwent upper abdomen MRI including DWI, liver-specific contrast agent-enhanced imaging, and 5-HTP PET/CT. RESULTS There was a patient-based concordance of 61% and a lesion-based concordance of 53% between the modalities. MRI showed good concordance with PET in detecting bone metastases but was less sensitive in detecting metastases in mediastinal lymph nodes. MRI detected more liver metastases than 5-HTP PET/CT. CONCLUSION Whole-body MRI with DWI did not detect all NET lesions found with whole-body 5-HTP PET/CT. Our findings indicate that MRI of the liver including liver-specific contrast agent-enhanced imaging and DWI could be a useful complement to whole-body 5-HTP PET/CT.
Collapse
Affiliation(s)
- Lina Carlbom
- Institute of Surgical Sciences, Department of Radiology, Uppsala University, Uppsala, Sweden
| | | | - Dan Granberg
- Department of Medical Sciences. Uppsala University, Uppsala, Sweden
| | - Jens Sörensen
- Institute of Surgical Sciences, Department of Radiology, Uppsala University, Uppsala, Sweden
| | - Barbro Eriksson
- Department of Medical Sciences. Uppsala University, Uppsala, Sweden
| | - Håkan Ahlström
- Institute of Surgical Sciences, Department of Radiology, Uppsala University, Uppsala, Sweden
- CONTACT Håkan Ahlström Institute of Surgical Sciences, Department of Radiology, Entrance 70, 2nd floor, Uppsala University, Uppsala University Hospital, SE-75185, Uppsala. Sweden
| |
Collapse
|
|
28
|
Abstract
Insulinomas are rare neuroendocrine tumors which occur predominantly in the pancreas. Although majority of the insulinomas are benign, over-secretion of insulin by the tumor leads to debilitating hypoglycemic symptoms. The diagnosis is based on clinical and biochemical findings. After the diagnosis is made, the principal challenge lies in locating the tumor because most tumors are solitary and small in size. Locating the tumor is of paramount importance as complete surgical excision is the only curative treatment, and incomplete resection leads to persistence of symptoms. Different preoperative and intraoperative imaging techniques have been used with varying success rates for the insulinoma imaging. Besides localizing the tumor, imaging also helps to guide biopsy, detect metastatic lesions, and perform image-guided therapeutic procedures. This review will discuss the role of different Cross sectional and nuclear medicine imaging modalities in insulinomas.
Collapse
|
|
29
|
Pelosi E, Deandreis D, Cassalia L, Penna D. Diagnostic Applications of Nuclear Medicine: Colorectal Cancer. NUCLEAR ONCOLOGY 2017:777-797. [DOI: 10.1007/978-3-319-26236-9_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
|
|
30
|
Tabacchi E, Nanni C, Bossert I, Maffione AM, Fanti S. Diagnostic Applications of Nuclear Medicine: Pancreatic Cancer. NUCLEAR ONCOLOGY 2017:749-775. [DOI: 10.1007/978-3-319-26236-9_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
31
|
Bodei L, Kidd M, Gilardi L, Volterrani D, Paganelli G, Grana CM, Modlin IM. Diagnostic Applications of Nuclear Medicine: Neuroendocrine Tumors. NUCLEAR ONCOLOGY 2017:799-838. [DOI: 10.1007/978-3-319-26236-9_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
32
|
Imaging approaches to assess the therapeutic response of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): current perspectives and future trends of an exciting field in development. Cancer Metastasis Rev 2016; 34:823-42. [PMID: 26433592 PMCID: PMC4661203 DOI: 10.1007/s10555-015-9598-5] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a family of neoplasms with a complex spectrum of clinical behavior. Although generally more indolent than carcinomas, once they progress beyond surgical resectability, they are essentially incurable. Systemic treatment options have substantially expanded in recent years for the management of advanced disease. Imaging plays a major role in new drug development, as it is the main tool used to objectively evaluate response to novel agents. However, current standard response criteria have proven suboptimal for the assessment of the antiproliferative effect of many targeted agents, particularly in the context of slow-growing tumors such as well-differentiated NETs. The aims of this article are to discuss the advantages and limitations of conventional radiological techniques and standard response assessment criteria and to review novel imaging modalities in development as well as alternative cancer- and therapy-specific criteria to assess drug efficacy in the field of GEP-NETs.
Collapse
|
|
33
|
Eriksson O, Selvaraju R, Eich T, Willny M, Brismar TB, Carlbom L, Ahlström H, Tufvesson G, Lundgren T, Korsgren O. Positron Emission Tomography to Assess the Outcome of Intraportal Islet Transplantation. Diabetes 2016; 65:2482-9. [PMID: 27325286 PMCID: PMC5001185 DOI: 10.2337/db16-0222] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2016] [Accepted: 06/10/2016] [Indexed: 11/25/2022]
Abstract
No imaging methodology currently exists to monitor viable islet mass after clinical intraportal islet transplantation. We investigated the potential of the endocrine positron emission tomography (PET) marker [(11)C]5-hydroxytryptophan ([(11)C]5-HTP) for this purpose. In a preclinical proof-of-concept study, the ex vivo and in vivo [(11)C]5-HTP signal was compared with the number of islets transplanted in rats. In a clinical study, human subjects with an intraportal islet graft (n = 8) underwent two [(11)C]5-HTP PET and MRI examinations 8 months apart. The tracer concentration in the liver as a whole, or in defined hotspots, was correlated to measurements of islet graft function. In rat, hepatic uptake of [(11)C]5-HTP correlated with the number of transplanted islets. In human subjects, uptake in hepatic hotspots showed a correlation with metabolic assessments of islet function. Change in hotspot standardized uptake value (SUV) predicted loss of graft function in one subject, whereas hotspot SUV was unchanged in subjects with stable graft function. The endocrine marker [(11)C]5-HTP thus shows a correlation between hepatic uptake and transplanted islet function and promise as a tool for noninvasive detection of viable islets. The evaluation procedure described can be used as a benchmark for novel agents targeting intraportally transplanted islets.
Collapse
Affiliation(s)
- Olof Eriksson
- Preclinical PET Platform, Department of Medical Chemistry, Uppsala University, Uppsala, Sweden
| | - Ramkumar Selvaraju
- Preclinical PET Platform, Department of Medical Chemistry, Uppsala University, Uppsala, Sweden
| | - Torsten Eich
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| | - Mariam Willny
- Preclinical PET Platform, Department of Medical Chemistry, Uppsala University, Uppsala, Sweden
| | - Torkel B Brismar
- Division of Medical Imaging and Technology, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Lina Carlbom
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Håkan Ahlström
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Gunnar Tufvesson
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Torbjörn Lundgren
- Division of Transplantation Surgery, CLINTEC, Karolinska Institutet, Stockholm, Sweden
| | - Olle Korsgren
- Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
| |
Collapse
|
|
34
|
Liu EH, Solorzano CC, Katznelson L, Vinik AI, Wong R, Randolph G. AACE/ACE disease state clinical review: diagnosis and management of midgut carcinoids. Endocr Pract 2016; 21:534-545. [PMID: 25962092 DOI: 10.4158/ep14464.dsc] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE Neuroendocrine tumors (NETs) are a collection of complex tumors that arise from the diffuse endocrine system, primarily from the digestive tract. Carcinoid tumors most commonly originate from the small intestine. These tumors are either referred to as small intestinal neuroendocrine tumors or midgut carcinoids (MGCs). The purpose of this review article is to survey the diagnostic and therapeutic pathways for patients with MGC and provide an overview of the complex multidisciplinary care involved in improving their quality of life, treatment outcomes, and survival. METHODS The current literature regarding the diagnosis and management of MGCs was reviewed. RESULTS Dry flushing and secretory diarrhea are the hallmarks of the clinical syndrome of MGC. Managing MGC requires attention to the overall symptom complex, including the physical effects of the tumor and biomarker levels. The somatostatin analogs (SAs) octreotide and lanreotide are highly efficacious for symptomatic improvement. MGCs require resection to encompass the primary tumor and mesenteric lymph node metastases and should include cholecystectomy if the patient is likely to receive SA therapy. Debulking of liver metastasis by resection in combination with ablative therapies and other liver-directed modalities may help palliate symptoms and hormonal overproduction in carefully selected patients. Quality of life is an important measure of patients' perception of the burden of their disease and impact of treatment modalities and may be a useful guide in deciding changes in therapy to alter apparent health status. CONCLUSION MGC is a challenging malignancy that requires the input of a multidisciplinary team to develop the best treatment plan. Consultation with expert centers that specialize in NETs may also be indicated for complex cases. With expert care, patients can be cured or live with the disease and enjoy good quality of life.
Collapse
Affiliation(s)
- Eric H Liu
- Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University, Nashville, Tennessee
| | - Carmen C Solorzano
- Division of Surgical Oncology and Endocrine Surgery, Vanderbilt University, Nashville, Tennessee
| | | | - Aaron I Vinik
- Department of Medicine, Eastern Virginia Medical School, Norfolk, Virginia
| | - Richard Wong
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Gregory Randolph
- Department of Otolaryngology, Massachusetts General Hospital, Boston, Massachusetts
| |
Collapse
|
|
35
|
Carbidopa-assisted 18F-fluorodihydroxyphenylalanine PET/CT for the localization and staging of non-functioning neuroendocrine pancreatic tumors. Ann Nucl Med 2016; 30:659-668. [PMID: 27485404 DOI: 10.1007/s12149-016-1110-y] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 07/27/2016] [Indexed: 12/11/2022]
Abstract
OBJECTIVE CD premedication was found to increase the value of 18F-fluorodihydroxyphenylalanine (18F-FDOPA) PET/CT imaging in the detection of adult insulinoma. The aim of this study was to evaluate the performance of CD-assisted 18F-FDOPA PET/CT in the diagnosis and staging of non-functioning pNETs. METHODS Twenty consecutive patients with low-grade pNETs who underwent CD-assisted 18F-FDOPA PET/CT imaging and 111In-somatostatin receptor scintigraphy (SRS) were evaluated. Histology was considered as the gold standard. In case where no surgical resection was performed, the diagnosis of pNET was made by the confrontation of the different available imaging modalities. RESULTS CD-assisted 18F-FDOPA PET/CT was positive in 18/20 cases (90 %), whereas SRS was positive in 13/19 cases (68 %). When considered the 19 patients underwent both nuclear medicine examinations, 18F-FDOPA PET/CT was significantly more sensitive then SRS for primary tumor detection (p = 0.049). False-negative results of both 18F-FDOPA PET/CT and SRS were observed in 2 cystic pNETs. SRS failed to detect one additional cystic tumor and 3 pNETs of 10, 12 and 17 mm, respectively. 18F-FDOPA PET/CT correctly identified all patients with lymphatic, visceral and bone metastases. SRS failed to detect lymphatic spread and was falsely negative in one patient with splenic metastasis. CONCLUSIONS Contrary to widely held assumptions, our study further expands the application of CD-assisted 18F-FDOPA PET/CT for non-functioning pNETs when 68Ga-radiolabeled somatostatin analogs are not available.
Collapse
|
|
36
|
Eriksson O, Laughlin M, Brom M, Nuutila P, Roden M, Hwa A, Bonadonna R, Gotthardt M. In vivo imaging of beta cells with radiotracers: state of the art, prospects and recommendations for development and use. Diabetologia 2016; 59:1340-1349. [PMID: 27094935 DOI: 10.1007/s00125-016-3959-7] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2016] [Accepted: 03/23/2016] [Indexed: 12/15/2022]
Abstract
Radiotracer imaging is characterised by high in vivo sensitivity, with a detection limit in the lower picomolar range. Therefore, radiotracers represent a valuable tool for imaging pancreatic beta cells. High demands are made of radiotracers for in vivo imaging of beta cells. Beta cells represent only a small fraction of the volume of the pancreas (usually 1-3%) and are scattered in the tiny islets of Langerhans throughout the organ. In order to be able to measure a beta cell-specific signal, one has to rely on highly specific tracer molecules because current in vivo imaging technologies do not allow the resolution of single islets in humans non-invasively. Currently, a considerable amount of preclinical data are available for several radiotracers and three are under clinical evaluation. We summarise the current status of the evaluation of these tracer molecules and put forward recommendations for their further evaluation.
Collapse
Affiliation(s)
- Olof Eriksson
- Preclinical PET Platform, Department of Medical Chemistry, Uppsala University, Dag Hammarskjölds väg 14C, 3tr, SE-751 83, Uppsala, Sweden.
- Turku PET Centre, University of Turku, Turku, Finland.
- Department of Biosciences, Åbo Akademi University, Turku, Finland.
| | - Maren Laughlin
- National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
| | - Maarten Brom
- Department of Radiology and Nuclear Medicine, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands
| | - Pirjo Nuutila
- Turku PET Centre, University of Turku, Turku, Finland
| | - Michael Roden
- Department of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany
- Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University, Düsseldorf, Germany
| | - Albert Hwa
- JDRF, Discovery Research, New York, NY, USA
| | - Riccardo Bonadonna
- Division of Endocrinology, Department of Clinical and Experimental Medicine, University of Parma and AOU of Parma, Parma, Italy
| | - Martin Gotthardt
- Department of Radiology and Nuclear Medicine, Radboud university medical center, PO Box 9101, 6500HB, Nijmegen, the Netherlands.
| |
Collapse
|
|
37
|
Chiotellis A, Müller Herde A, Rössler SL, Brekalo A, Gedeonova E, Mu L, Keller C, Schibli R, Krämer SD, Ametamey SM. Synthesis, Radiolabeling, and Biological Evaluation of 5-Hydroxy-2-[18F]fluoroalkyl-tryptophan Analogues as Potential PET Radiotracers for Tumor Imaging. J Med Chem 2016; 59:5324-40. [DOI: 10.1021/acs.jmedchem.6b00057] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Affiliation(s)
- Aristeidis Chiotellis
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| | - Adrienne Müller Herde
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| | - Simon L. Rössler
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| | - Ante Brekalo
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| | - Erika Gedeonova
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| | - Linjing Mu
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Department of Nuclear
Medicine, University Hospital Zurich, Zurich 8091, Switzerland
| | - Claudia Keller
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| | - Roger Schibli
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| | - Stefanie D. Krämer
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| | - Simon M. Ametamey
- Center
for Radiopharmaceutical Sciences ETH-PSI-USZ, Institute of Pharmaceutical Sciences ETH, Vladimir-Prelog-Weg 1-5/10, Zurich 8093, Switzerland
| |
Collapse
|
|
38
|
Xavier S, Rosa B, Cotter J. Small bowel neuroendocrine tumors: From pathophysiology to clinical approach. World J Gastrointest Pathophysiol 2016; 7:117-124. [PMID: 26909234 PMCID: PMC4753177 DOI: 10.4291/wjgp.v7.i1.117] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2015] [Revised: 09/09/2015] [Accepted: 12/18/2015] [Indexed: 02/06/2023] Open
Abstract
Neuroendocrine tumors (NETs), defined as epithelial tumors with predominant neuroendocrine differentiation, are among the most frequent types of small bowel neoplasm. They represent a rare, slow-growing neoplasm with some characteristics common to all forms and others attributable to the organ of origin. The diagnosis of this subgroup of neoplasia is not usually straight-forward for several reasons. Being a rare form of neoplasm they are frequently not readily considered in the differential diagnosis. Also, clinical manifestations are nonspecific lending the clinician no clue that points directly to this entity. However, the annual incidence of NETs has risen in the last years to 40 to 50 cases per million probably not due to a real increase in incidence but rather due to better diagnostic tools that have become progressively available. Being a rare malignancy, investigation regarding its pathophysiology and efforts toward better understanding and classification of these tumors has been limited until recently. Clinical societies dedicated to this matter are emerging (NANETS, ENETS and UKINETS) and several guidelines were published in an effort to standardize the nomenclature, grading and staging systems as well as diagnosis and management of NETs. Also, some investigation on the genetic behavior of small bowel NETs has been recently released, shedding some light on the pathophysiology of these tumors, and pointing some new directions on the possible treating options. In this review we focus on the current status of the overall knowledge about small bowel NETs, focusing on recent breakthroughs and its potential application on clinical practice.
Collapse
|
|
39
|
Niederle B, Pape UF, Costa F, Gross D, Kelestimur F, Knigge U, Öberg K, Pavel M, Perren A, Toumpanakis C, O'Connor J, O'Toole D, Krenning E, Reed N, Kianmanesh R. ENETS Consensus Guidelines Update for Neuroendocrine Neoplasms of the Jejunum and Ileum. Neuroendocrinology 2016; 103:125-38. [PMID: 26758972 DOI: 10.1159/000443170] [Citation(s) in RCA: 331] [Impact Index Per Article: 36.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- B Niederle
- Department of Surgery, Medical University of Vienna, Vienna, Austria
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
40
|
Abstract
Neuroendocrine tumors (NETs) are slow-growing neoplasms capable of storing and secreting different peptides and neuroamines. Some of these substances cause specific symptom complexes, whereas others are silent. They usually have episodic expression, and the diagnosis is often made at a late stage. Although considered rare, the incidence of NETs is increasing. For these reasons, a high index of suspicion is needed. In this article, the different clinical syndromes and the pathophysiology of each tumor as well as the new and emerging biochemical markers and imaging techniques that should be used to facilitate an early diagnosis, follow-up, and prognosis are reviewed.
Collapse
|
|
41
|
Sato S, Kitahara A, Koike T, Hashimoto T, Ohashi R, Kameda Y, Tsuchida M. A Case of Ectopic ACTH-Producing Pulmonary Carcinoid Arising in an Extralobar Pulmonary Sequestration. Int J Surg Pathol 2015; 24:130-4. [PMID: 26378053 DOI: 10.1177/1066896915605615] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Ectopic adrenocorticotrophic hormone (ACTH)-producing bronchopulmonary carcinoid arising in a bronchopulmonary sequestration is extremely rare. The case of a 67-year-old woman with a 1.7-cm nodule in the mediastinal side of the left lower lobe is presented. At 52 years of age, she was diagnosed as having ACTH-dependent Cushing's syndrome (CS). However, no ectopic source of ACTH-secretion was detected. Seven years later, she underwent a bilateral adrenalectomy because of aggravation of her health condition. This time, tumor excision was performed by thoracoscopic surgery. The tumor adhered sparsely to the mediastinal pleura and the left lower lobe and was bluntly separated from these tissues. Pathologically, the tumor was a typical carcinoid arising in an extralobar pulmonary sequestration. Immunohistochemical staining confirmed the secretion of ACTH by bronchopulmonary carcinoid tumor cells. After surgery, the serum ACTH level was almost normalized, and the dexamethasone (1 mg) suppression test showed significant suppression of ACTH.
Collapse
Affiliation(s)
- Seijiro Sato
- Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Akihiko Kitahara
- Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Terumoto Koike
- Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Takehisa Hashimoto
- Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | - Riuko Ohashi
- Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| | | | - Masanori Tsuchida
- Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
| |
Collapse
|
|
42
|
Caplin ME, Baudin E, Ferolla P, Filosso P, Garcia-Yuste M, Lim E, Oberg K, Pelosi G, Perren A, Rossi RE, Travis WD. Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids. Ann Oncol 2015; 26:1604-1620. [PMID: 25646366 DOI: 10.1093/annonc/mdv041] [Citation(s) in RCA: 453] [Impact Index Per Article: 45.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2014] [Accepted: 01/22/2015] [Indexed: 12/20/2022] Open
Abstract
BACKGROUND Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management. PATIENTS AND METHODS Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review. RESULTS PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit. CONCLUSIONS PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.
Collapse
Affiliation(s)
- M E Caplin
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK
| | - E Baudin
- Department of Nuclear Medicine, Endocrine Cancer and Interventional Radiology, Institut Gustave Roussy, Université Paris Sud, Villejuif Cedex, France
| | - P Ferolla
- NET Center, Umbria Regional Cancer Network, Università degli Studi di Perugia, Perugia
| | - P Filosso
- Department of Thoracic Surgery, University of Torino, Torino, Italy
| | - M Garcia-Yuste
- Department of Thoracic Surgery, University Clinic Hospital, Valladolid, Spain
| | - E Lim
- Imperial College and The Academic Division of Thoracic Surgery, The Royal Brompton Hospital, London, UK
| | - K Oberg
- Endocrine Oncology Unit, Department of Medicine, University Hospital, Uppsala, Sweden
| | - G Pelosi
- Fondazione IRCCS Istituto Nazionale dei Tumori and Dipartimento di Scienze Biologiche e Cliniche Luigi Sacco, Università degli studi di Milano, Milan, Italy
| | - A Perren
- Institute of Pathology, University of Bern, Bern, Switzerland
| | - R E Rossi
- Neuroendocrine Tumour Unit, Royal Free Hospital, London, UK Gastroenterology and Endoscopy Unit, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico and Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy
| | - W D Travis
- Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, USA
| |
Collapse
|
|
43
|
Karlsson F, Antonodimitrakis PC, Eriksson O. Systematic screening of imaging biomarkers for the Islets of Langerhans, among clinically available positron emission tomography tracers. Nucl Med Biol 2015; 42:762-9. [PMID: 26138288 DOI: 10.1016/j.nucmedbio.2015.06.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Revised: 05/24/2015] [Accepted: 06/05/2015] [Indexed: 01/08/2023]
Abstract
INTRODUCTION Functional imaging could be utilized for visualizing pancreatic islets of Langerhans. Therefore, we present a stepwise algorithm for screening of clinically available positron emission tomography (PET) tracers for their use in imaging of the neuroendocrine pancreas in the context of diabetes. METHODS A stepwise procedure was developed for screening potential islet imaging agents. Suitable PET-tracer candidates were identified by their molecular mechanism of targeting. Clinical abdominal examinations were retrospectively analyzed for pancreatic uptake and retention. The target protein localization in the pancreas was assessed in silico by -omics approaches and the in vitro by binding assays to human pancreatic tissue. RESULTS Six putative candidates were identified and screened by using the stepwise procedure. Among the tested PET tracers, only [(11)C]5-Hydroxy-tryptophan passed all steps. The remaining identified candidates were falsified as candidates and discarded following in silico and in vitro screening. CONCLUSIONS Of the six clinically available PET tracers identified, [(11)C]5-HTP was found to be a promising candidate for beta cell imaging, based on intensity of in vivo pancreatic uptake in humans, and islet specificity as assessed on human pancreatic cell preparations. The flow scheme described herein constitutes a methodology for evaluating putative islet imaging biomarkers among clinically available PET tracers.
Collapse
Affiliation(s)
- Filip Karlsson
- Preclinical PET Platform, department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden
| | | | - Olof Eriksson
- Preclinical PET Platform, department of Medicinal Chemistry, Uppsala University, Uppsala, Sweden.
| |
Collapse
|
|
44
|
Abstract
Radionuclides are needed both for nuclear medicine imaging as well as for peptide-receptor radionuclide therapy (PRRT) of neuroendocrine tumors (NET). Imaging is important in the initial diagnostic work-up and for staging NETs. In therapy planning, somatostatin receptor imaging (SRI) is used when treatment is targeted at the somatostatin receptors as with the use of somatostatin analogues or PRRT. SRI with gamma camera technique using the tracer (111)In-DTPA-octreotide has for many years been the backbone of nuclear imaging of NETs. However, increasingly PET tracers for SRI are now used. (68)Ga-DOTATATE, (68)Ga-DOTATOC and (68)Ga-DOTANOC are the three most often used PET tracers. They perform better than SPECT tracers and should be preferred. FDG-PET is well suited for visualization of most of the somatostatin receptor-negative tumors prognostic in NET patients. Also (11)C-5-HTP, (18)F-DOPA and (123)I-MIBG may be used in NET. However, with FDG-PET and somatostatin receptor PET at hand we see limited necessity of other tracers. PRRT is an important tool in the treatment of advanced NETs causing complete or partial response in 20% and minor response or tumor stabilization in 60% with response duration of up to 3 years. Grade 3-4 kidney or bone marrow toxicity is seen in 1.5% and 9.5%, respectively, but are completely or partly reversible in most patients. (177)Lu-DOTATATE seems to have less toxicity than (90)Y-DOTATOC. However, until now only retrospective, non-randomized studies have been performed and the role of PRRT in treatment of NETs remains to be established.
Collapse
Affiliation(s)
- Andreas Kjaer
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Copenhagen, Denmark,European NET Centre of Excellence, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark,Correspondence: Andreas Kjaer, Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Rigshospitalet and University of Copenhagen, Denmark.
| | - Ulrich Knigge
- Department of Clinical Physiology, Nuclear Medicine & PET and Cluster for Molecular Imaging, Copenhagen, Denmark,Departments of Surgery Cand Endocrinology PE, Copenhagen, Denmark,European NET Centre of Excellence, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| |
Collapse
|
|
45
|
Öberg K. Neuroendocrine gastro-enteropancreatic tumors - from eminence based to evidence-based medicine - A Scandinavian view. Scand J Gastroenterol 2015; 50:727-39. [PMID: 25855088 DOI: 10.3109/00365521.2015.1033001] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Neuroendocrine tumors (NETs) comprise a heterogenous group of neoplasms with variable clinical expression and progression. The primary tumors most frequently occur in the lungs, intestine and the pancreas. The NET incidence is approximately 6.1/100,000 per year with a prevalence higher than 35/100,000 per year. A NET may be functioning with symptoms related to hormone overproduction or non-functioning, not presenting any hormone-related symptoms. From the early 1980s and onwards, Uppsala University Hospital has contributed significantly to diagnosis, just to mention immunohistochemistry, radio-immunoassays for hormones and peptides and molecular imaging. On the therapeutic side, treatments with cytotoxics as well as biologicals such as, somatostatin analogs and interferons have been evaluated. We have furthermore been involved in important phase III trials for registration of so called, new targeted agents such as, RADIANT-3 and RADIANT-2. Our group were also the first to localize the gene for MEN I on chromosome 11 locus q13. Most recent developments have been the establishments of new biomarkers such as, olfactory receptor E51E1 as well as micro-RNAs in carcinoid tumors of the intestine and lung. A new oncolytic virus, Ad-Vince, for treatment of most NETs has been developed and is ready for the clinic. Furthermore, we have been involved in establishing Nordic and international collaborations. Today, NETs is an area with rapid development and recognized by international organizations at conferences, with large attendance. The Nordic countries continue to be significant contributors to the field.
Collapse
Affiliation(s)
- Kjell Öberg
- Department of Endocrine Oncology, Uppsala University Hospital , Entrance 40, 5th floor, SE-751 85 Uppsala , Sweden
| |
Collapse
|
|
46
|
Sharma ST, Nieman LK, Feelders RA. Cushing's syndrome: epidemiology and developments in disease management. Clin Epidemiol 2015; 7:281-93. [PMID: 25945066 PMCID: PMC4407747 DOI: 10.2147/clep.s44336] [Citation(s) in RCA: 97] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Cushing’s syndrome is a rare disorder resulting from prolonged exposure to excess glucocorticoids. Early diagnosis and treatment of Cushing’s syndrome is associated with a decrease in morbidity and mortality. Clinical presentation can be highly variable, and establishing the diagnosis can often be difficult. Surgery (resection of the pituitary or ectopic source of adrenocorticotropic hormone, or unilateral or bilateral adrenalectomy) remains the optimal treatment in all forms of Cushing’s syndrome, but may not always lead to remission. Medical therapy (steroidogenesis inhibitors, agents that decrease adrenocorticotropic hormone levels or glucocorticoid receptor antagonists) and pituitary radiotherapy may be needed as an adjunct. A multidisciplinary approach, long-term follow-up, and treatment modalities customized to each individual are essential for optimal control of hypercortisolemia and management of comorbidities.
Collapse
Affiliation(s)
- Susmeeta T Sharma
- Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - Lynnette K Nieman
- Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
| | - Richard A Feelders
- Division of Endocrinology, Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands
| |
Collapse
|
|
47
|
Abstract
Diagnosis of Cushing's disease frequently remains a challenge. In this review we critically appraise the clinical features, biochemical tests, and imaging modalities used for this purpose. We outline recommendations for approaches to clinical investigation, with a particular focus on developments made within the last two years.
Collapse
Affiliation(s)
- Eleni Daniel
- Academic Unit of Endocrinology, University of Sheffield, Beech Hill Road, Sheffield, S10 2RX, UK
| | | |
Collapse
|
|
48
|
James PD, Tsolakis AV, Zhang M, Belletrutti PJ, Mohamed R, Roberts DJ, Heitman SJ. Incremental benefit of preoperative EUS for the detection of pancreatic neuroendocrine tumors: a meta-analysis. Gastrointest Endosc 2015; 81:848-56.e1. [PMID: 25805462 DOI: 10.1016/j.gie.2014.12.031] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/14/2014] [Accepted: 12/01/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND Current guidelines recommend CT scan or magnetic resonance imaging as the initial imaging modalities for the work-up of suspected pancreatic neuroendocrine tumors (PNETs). OBJECTIVE To determine the incremental benefit of preoperative EUS (IBEUS) for the detection of suspected PNETs after other investigative modalities have been attempted. DESIGN This systematic review searched MEDLINE, EMBASE, bibliographies of included articles, and conference proceedings for studies reporting original data regarding the preoperative detection of PNETs. Pooled IBEUS was calculated by using random effects models. Heterogeneity was explored by using stratified meta-analysis and meta-regression. Evidence of small-study effects was assessed by using funnel plots and the Begg test. PATIENTS Patients with suspected PNETs. INTERVENTIONS EUS evaluation. MAIN OUTCOME MEASUREMENTS The pooled IBEUS for the detection of PNETs after CT scan, with or without additional investigative modalities. RESULTS Among 4505 citations identified, we included 17 cohort studies (612 patients). EUS identified PNETs in 97% of cases. Improved PNET identification with EUS was observed in all of the studies. After adjusting for small-study effects, meta-analysis showed that EUS alone could identify PNETs in approximately 1 in 4 patients (adjusted IBEUS 26%; 95% confidence interval, 17%-37%). The pooled IBEUS varied based on the study design, study size, type of CT scan used, and the number of modalities used prior to EUS. LIMITATIONS The majority of included studies were retrospective. Small-study effects were observed. CONCLUSION Preoperative EUS is associated with an increase in PNET detection after other modalities are attempted.
Collapse
Affiliation(s)
- Paul D James
- Department of Medicine and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Ontario, Canada; Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Apostolos V Tsolakis
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada; Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - Mei Zhang
- Department of Medical Sciences, Section of Endocrine Oncology, Uppsala University, Uppsala, Sweden
| | - Paul J Belletrutti
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Rachid Mohamed
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Derek J Roberts
- Department of Surgery and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| | - Steven J Heitman
- Department of Medicine and Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
| |
Collapse
|
|
49
|
Sowa‐Staszczak A, Stefańska A, Jabrocka‐Hybel A, Hubalewska‐Dydejczyk A. Somatostatin Receptor Scintigraphy in Management of Patients with Neuroendocrine Neoplasms. SOMATOSTATIN ANALOGUES 2015:90-111. [DOI: 10.1002/9781119031659.ch9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
50
|
Yang K, Cheng YS, Yang JJ, Jiang X, Guo JX. Primary hepatic neuroendocrine tumor with multiple liver metastases: A case report with review of the literature. World J Gastroenterol 2015; 21:3132-3138. [PMID: 25780316 PMCID: PMC4356938 DOI: 10.3748/wjg.v21.i10.3132] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2014] [Revised: 10/26/2014] [Accepted: 11/07/2014] [Indexed: 02/06/2023] Open
Abstract
We herein present a case involving a 41-year-old woman in whom ultrasound examination revealed multiple liver hemangiomas more than 3 years ago. Follow-up ultrasound examination revealed that the masses had significantly increased; the largest was located in the right lobe (about 8.2 cm × 7.4 cm × 6.0 cm). Abdominal multidetector computed tomography revealed multiple well-circumscribed, heterogeneous, hypodense masses (largest, 6.4 cm × 6.3 cm × 5.0 cm) with significant contrast enhancement during the arterial and portal phases and with contrast wash-out and peripheral enhancement during the delayed phases. Magnetic resonance images demonstrated multiple well-circumscribed, heterogeneous, hypointense hepatic masses with significant contrast enhancement (largest, 6.4 cm × 6.5 cm × 5.1 cm); multiple enlarged porta lymph nodes; and multiple slightly enlarged retroperitoneal lymph nodes. Histological and immunohistochemical examination of the right mass biopsy specimen suggested a malignant neoplasm that had originated from a neuroendocrine cell type (grade 2 well-differentiated neuroendocrine carcinoma). After performing a systemic examination to exclude metastasis from an extrahepatic primary site, we considered that the masses had arisen from a primary hepatic neuroendocrine tumor with multiple liver metastases. The patient underwent transcatheter arterial chemoembolization using a combination of oxaliplatin (150 mg) mixed with one bottle of gelatin sponge particles (560-710 μm) and lipiodol (6 mL). Primary neuroendocrine tumors of the liver are extremely rare. This case is interesting because of the rarity of this neoplasm and previous misdiagnosis as multiple liver hemangiomas. Previously reported cases in the literature are also reviewed.
Collapse
|