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Peng Y, Liu H, Miao M, Cheng X, Chen S, Yan K, Mu J, Cheng H, Liu G. Micro-Nano Convergence-Driven Radiotheranostic Revolution in Hepatocellular Carcinoma. ACS APPLIED MATERIALS & INTERFACES 2025; 17:29047-29081. [PMID: 40347149 DOI: 10.1021/acsami.5c05525] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/12/2025]
Abstract
Radiotherapy, as an important means of treating hepatocellular carcinoma (HCC), has shown unique therapeutic advantages, especially in patients who are unable to undergo surgery or transplantation. It mainly includes external radiotherapy, transarterial radioembolization and intratumoral radioactive particle implantation. However, under the influence of factors such as the hypoxic characteristics of the liver tumor microenvironment and the radioresistance of tumor cells, the effect of radiotherapy may be unstable and may cause side effects, affecting the quality of life of patients. In recent years, with the development of nanotechnology, drug delivery systems based on micro-nanomaterials have provided new solutions for improving the effect of radiotherapy for HCC. Despite this, the application of micro-nano drug delivery systems in the treatment of HCC still faces some challenges, mainly including the in vivo safety and in vivo metabolism of micro-nano materials. This article reviews the latest progress of micro-nano materials in the treatment of HCC, especially their application in radiosensitization and their clinical translation potential. This article systematically analyzes the role of micro-nanomaterials in external or internal radiotherapy sensitization and radioimmunotherapy and explores the advantages of micro-nanomaterials in improving the treatment effect of HCC.
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Affiliation(s)
- Yisheng Peng
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Hui Liu
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Mengmeng Miao
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Xu Cheng
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Shangqing Chen
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Kaifei Yan
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
| | - Jing Mu
- Institute of Precision Medicine, Peking University Shenzhen Hospital, Shenzhen 518036, China
| | - Hongwei Cheng
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
- Zhuhai UM Science & Technology Research Institute, University of Macau, Macau SAR 999078, China
| | - Gang Liu
- State Key Laboratory of Vaccine for Infectious Diseases, Xiang An Biomedicine Laboratory, National Innovation Platform for Industry-Education Integration in Vaccine Research, State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen 361102, China
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Nault JC, Boubaya M, Wartski M, Dohan A, Pol S, Pop G, Soussan M, Sutter O, Costentin C, Roux J, Sengel C, Lequoy M, Montravers F, Menu Y, Pageaux GP, Goulart DM, Guiu B, Luciani A, Nahon P, Dioguardi Burgio M, Wagner M, Maksud P, Mulé S, Allaire M, Sidali S, Coilly A, Besson FL, Lewin M, Regnault H, Hollande C, Amaddeo G, Ronot M, Ganne-Carrié N, Itti E, Bloch-Queyrat C, Levy V, Lebtahi R, Chalaye J, Bouattour M. [ 18F]fluorodeoxyglucose and [ 18F]fluorocholine PET-CT for staging optimisation and treatment modification in hepatocellular carcinoma (PET-HCC01): a prospective multicentre study. Lancet Gastroenterol Hepatol 2025; 10:306-314. [PMID: 39987937 DOI: 10.1016/s2468-1253(25)00011-1] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Revised: 01/11/2025] [Accepted: 01/13/2025] [Indexed: 02/25/2025]
Abstract
BACKGROUND The role of PET-CT with [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluorocholine ([18F]FCH) in staging hepatocellular carcinoma and treatment decisions has, to our knowledge, never been prospectively assessed. METHODS We conducted a multicentre prospective study (PET-HCC01) in nine hospitals in France, including patients aged 18 years or older with a first diagnosis of hepatocellular carcinoma classified as Barcelona Clinic Liver Cancer (BCLC) classification A to C (without metastasis). At study inclusion, patients underwent contrast-enhanced liver MRI and liver, chest, and pelvis CT scans. Patients subsequently underwent [18F]FCH and [18F]FDG PET-CT. A first tumour staging and treatment decision was recorded by the multidisciplinary tumour board at each centre using morphological imaging, blind to the results of the PET-CTs. After the results of the PET-CTs were revealed, a second tumour staging and treatment decision was recorded. The primary endpoint was the proportion of patients whose treatment was modified by PET-CTs. Analyses were done in the intention-to-image population, consisting of all patients who had undergone at least one PET-CT and were discussed by the multidisciplinary tumour board. This study was registered with ClinicalTrials.gov, NCT04391348. FINDINGS Between July 20, 2020, and April 27, 2023, 230 patients were enrolled. Among the 215 patients included in the intention-to-image population, the median age was 66·0 years (IQR 60·0-71·5), 193 (90%) were male, and 155 (73%) had cirrhosis. Hepatocellular carcinoma was classified as BCLC stage A in 140 (65%) patients, B in 48 (22%), and C without metastasis in 27 (13%) on the basis of morphological imaging. Potential new lesions were identified in 19 (9%) patients by PET-CT (eight by both tracers, six by [18F]FCH only, and five by [18F]FDG only) and in six of these patients, follow-up confirmed the diagnosis of hepatocellular carcinoma (one lesion in the adrenal gland, two in bones, two in the lymph node, and one intrahepatic). PET-CT modified BCLC stage in ten patients: disease stage for two patients moved from BCLC A to B, from BCLC A to C for two patients, from BCLC B to C for two patients, and from BCLC C without metastasis to BCLC C with metastasis for four patients. Planned treatment was modified for four patients (2% [95% CI 1-5]), below the prespecified threshold of clinical significance (10%). INTERPRETATION [18F]FDG and [18F]FCH-PET-CTs should not be systematically performed for staging a first diagnosis of hepatocellular carcinoma, as they modified treatment decisions only in a minority of patients. FUNDING Programme Hospitalier de Recherche Clinique Inter-regional-PHRC-I2018 (Ministère de la Santé).
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Affiliation(s)
- Jean-Charles Nault
- Service d'Hépatologie, Hôpital Avicenne, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, Functional Genomics of Solid Tumors, Paris, France.
| | | | - Myriam Wartski
- Department of Nuclear Medicine, Hôpital Cochin, AP-HP, Paris, France
| | - Anthony Dohan
- Department of Radiology, Hôpital Cochin, AP-HP, Paris, France; Université Paris Cité, Faculté de Médecine, Paris, France
| | - Stanislas Pol
- Centre Université Paris Centre, Groupe Hospitalier Cochin Port Royal, AP-HP, DMU Cancérologie et spécialités médico-chirurgicales, Service des Maladies du foie, Université Paris Cité, Paris, France
| | - Gabriel Pop
- Université Paris 13, AP-HP, Service de Médecine nucléaire, Hôpital universitaire Avicenne, Bobigny, France
| | - Michael Soussan
- Université Paris 13, AP-HP, Service de Médecine nucléaire, Hôpital universitaire Avicenne, Bobigny, France
| | - Olivier Sutter
- Interventional Radiology Unit, Hôpital Avicenne, Hôpitaux Universitaires Paris-Seine-Saint-Denis, AP-HP, Bobigny, France
| | - Charlotte Costentin
- Institute for Advanced Biosciences, Research Center UGA/Inserm U 1209/CNRS 5309; Gastroenterology, hepatology and GI oncology department, Digidune, Grenoble Alpes University Hospital, La Tronche, France
| | - Julie Roux
- Department of Nuclear Medicine, Grenoble Alpes University Hospital, Grenoble, France
| | - Christian Sengel
- Department of Radiology, Grenoble Alpes University Hospital, Grenoble, France
| | - Marie Lequoy
- Hepatology Department, Saint Antoine Hospital, AP-HP, Paris, France; INSERM UMRS 938 - Centre de Recherche Saint Antoine, APHP Sorbonne Université, Paris, France
| | | | - Yves Menu
- Département d'imagerie, Gustave Roussy, Villejuif, France; SIRIC CURAMUS, INSERM, Unité Mixte de Recherche Scientifique 938, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Equipe Labellisée par la Ligue Nationale Contre le Cancer, Paris, France
| | | | - Denis Mariano Goulart
- Department of Nuclear Medicine, CHU of Montepellier, PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France
| | - Boris Guiu
- Department of Radiology, St-Eloi University Hospital, Montpellier, France
| | - Alain Luciani
- Université Paris-Est Créteil, Créteil, France; INSERM, U955, Virus Hépatologie Cancer, Créteil, France; Department of Medical Imaging, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Pierre Nahon
- Service d'Hépatologie, Hôpital Avicenne, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, Functional Genomics of Solid Tumors, Paris, France
| | - Marco Dioguardi Burgio
- Department of Radiology, Hôpital Beaujon, AP-HP Nord, Paris, France; INSERM U1149 Centre de Recherche sur l'Inflammation, Université Paris Cité, Paris, France
| | - Mathilde Wagner
- Department of Radiology, Hospital Pitié Salpêtrière, Paris; UMR 7371, Université Sorbonne, CNRS, Inserm U114615, rue de l'École de Médecine, 75006, Paris, France
| | - Philippe Maksud
- Service de médecine nucléaire, AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Paris, France
| | - Sebastien Mulé
- Université Paris-Est Créteil, Créteil, France; INSERM, U955, Virus Hépatologie Cancer, Créteil, France; Department of Medical Imaging, Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Créteil, France
| | - Manon Allaire
- Service d'Hépato-gastroentérologie, AP-HP Sorbonne Université, Hôpital Universitaire Pitié-Salpêtrière, Paris, France; INSERM UMR 1138, Centre de recherche des Cordeliers, Paris, France
| | - Sabrina Sidali
- Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, Functional Genomics of Solid Tumors, Paris, France; Liver Unit, Paris Cité University, Beaujon Hospital, APHP, DMU DIGEST, Clichy, France
| | - Audrey Coilly
- Centre Hépato-Biliaire, AP-HP, Hôpital Paul Brousse, Villejuif, France; Université Paris-Saclay, INSERM, UMR_S 1193, Hepatinov, Orsay, France
| | - Florent L Besson
- Department of Nuclear Medicine-Molecular Imaging, Hôpitaux Universitaires Paris-Saclay, AP-HP, DMU SMART IMAGING, CHU Bicêtre, Le Kremlin-Bicêtre, France; Université Paris-Saclay, Commissariat à l'énergie atomique et aux énergies alternatives, Centre National de la Recherche Scientifique, Inserm, BioMaps, Orsay, France; Université Paris-Saclay, School of Medicine, Le Kremlin-Bicêtre, France
| | - Maïté Lewin
- Department of Radiology, Paul Brousse University Hospital, AP-HP-University Paris Saclay, Villejuif, France
| | - Hélène Regnault
- Hepatology Department, Henri Mondor Hospital, AP-HP, Créteil, France; Virus Hépatologie Cancer, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor, AP-HP, Université Paris-Est, Créteil, France
| | - Clémence Hollande
- Centre Université Paris Centre, Groupe Hospitalier Cochin Port Royal, AP-HP, DMU Cancérologie et spécialités médico-chirurgicales, Service des Maladies du foie, Université Paris Cité, Paris, France
| | - Giuliana Amaddeo
- Hepatology Department, Henri Mondor Hospital, AP-HP, Créteil, France; Virus Hépatologie Cancer, Institut Mondor de Recherche Biomédicale, INSERM U955, Hôpital Henri Mondor, AP-HP, Université Paris-Est, Créteil, France
| | - Maxime Ronot
- Department of Radiology, Hôpital Beaujon, AP-HP Nord, Paris, France; INSERM U1149 Centre de Recherche sur l'Inflammation, Université Paris Cité, Paris, France
| | - Nathalie Ganne-Carrié
- Service d'Hépatologie, Hôpital Avicenne, Bobigny, France; Unité de Formation et de Recherche Santé Médecine et Biologie Humaine, Université Paris 13, Communauté d'Universités et Etablissements Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Sorbonne Université, INSERM, Université de Paris, Functional Genomics of Solid Tumors, Paris, France
| | - Emmanuel Itti
- Nuclear Medicine Department, Henri Mondor Hospital, AP-HP, Créteil, France
| | | | - Vincent Levy
- URC-CRC GHPSS, Hôpital Avicenne, AP-HP, Bobigny, France
| | - Rachida Lebtahi
- Department of Nuclear Medicine, Hôpital Beaujon, AP-HP Nord, Paris, France; DMU DIGEST, Hôpital Beaujon, AP-HP Nord, Paris, France; Université Paris Cité, INSERM U1149, Centre de Recherche sur l'Inflammation, Paris, France
| | - Julia Chalaye
- Nuclear Medicine Department, Henri Mondor Hospital, AP-HP, Créteil, France
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Bucalau AM, Collette B, Tancredi I, Vierasu I, Tannouri F, Pezzullo M, Moreno-Reyes R, Verset G. 166Ho-RadioEmbolizaTiOn Using personalized prediCtive dosimetry in patients with Hepatocellular carcinoma: A prospective, single-centre study (RETOUCH). Liver Int 2025; 45:e15923. [PMID: 39569818 DOI: 10.1111/liv.15923] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 02/28/2024] [Accepted: 03/21/2024] [Indexed: 11/22/2024]
Abstract
BACKGROUND AND AIMS Holmium-166 (166Ho) radioembolization could offer a more individualized approach in terms of imaging and dosimetry. We aim to evaluate the feasibility and safety of 166Ho selective internal radiation therapy (SIRT) using a higher tumour dose than previously administered determined by 166Ho-scout as a surrogate marker in HCC patients. METHODS This is an open-label, prospective, non-randomized, single-centre pilot study that included patients with HCC that received 166Ho-SIRT if the work-up using 166Ho-scout showed a tumour-absorbed dose ≥150 Gy, a non-tumoural liver absorbed dose less than 60 Gy and a lung absorbed dose less than 30 Gy. Primary endpoints were feasibility and safety-toxicity profiles at 24-48 h and 1 month. Overall response rates (ORR) at 3 months (mRECIST, RECIST 1.1 and metabolic response by FDG and choline PET CT) and time to progression (TTP) represented the secondary endpoints. RESULTS Fifteen patients with large tumours (mean diameter 55.67 ± 28.42 mm) received 17 166Ho-SIRT treatments between July 2020 and June 2022. All the attempted treatments were accomplished. Mean administered tumour dose was 183.18 ± 71.71 Gy, while non-tumour liver dose was 30.29 ± 14.56 Gy. Median time of follow-up was 12 months (IQR 9-16). Only grade 1-2 clinical and biological AEs were observed. There were no liver decompensations. At 3 months, objective response was achieved for all target lesions (CR 78.57%, PR 21.43% according to mRECIST). Median TTP was 18.8 (range 2.9; n.e.) months. CONCLUSION Personalized 166Ho-SIRT with a tumour delivered dose ≥150 Gy was feasible and safe for HCC patients with promising response rates.
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Affiliation(s)
- Ana-Maria Bucalau
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Benoît Collette
- Department of Nuclear Medicine, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
- Laboratory of Image Synthesis and Analysis, Brussels School of Engineering, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Illario Tancredi
- Department of Radiology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Irina Vierasu
- Department of Nuclear Medicine, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Fadi Tannouri
- Department of Radiology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Martina Pezzullo
- Department of Radiology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Rodrigo Moreno-Reyes
- Department of Nuclear Medicine, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Gontran Verset
- Department of Gastroenterology, Hepatopancreatology and Digestive Oncology, Hôpital Universitaire de Bruxelles (HUB), Université libre de Bruxelles (ULB), Brussels, Belgium
- Medical Oncology Department, Institut Paoli-Calmettes Marseille, Marseille, France
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Sangro B, Argemi J, Ronot M, Paradis V, Meyer T, Mazzaferro V, Jepsen P, Golfieri R, Galle P, Dawson L, Reig M. EASL Clinical Practice Guidelines on the management of hepatocellular carcinoma. J Hepatol 2025; 82:315-374. [PMID: 39690085 DOI: 10.1016/j.jhep.2024.08.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2024] [Accepted: 08/29/2024] [Indexed: 12/19/2024]
Abstract
Liver cancer is the third leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 90% of primary liver cancers. Advances in diagnostic and therapeutic tools, along with improved understanding of their application, are transforming patient treatment. Integrating these innovations into clinical practice presents challenges and necessitates guidance. These clinical practice guidelines offer updated advice for managing patients with HCC and provide a comprehensive review of pertinent data. Key updates from the 2018 EASL guidelines include personalised surveillance based on individual risk assessment and the use of new tools, standardisation of liver imaging procedures and diagnostic criteria, use of minimally invasive surgery in complex cases together with updates on the integrated role of liver transplantation, transitions between surgical, locoregional, and systemic therapies, the role of radiation therapies, and the use of combination immunotherapies at various stages of disease. Above all, there is an absolute need for a multiparametric assessment of individual risks and benefits, considering the patient's perspective, by a multidisciplinary team encompassing various specialties.
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van der Aa DC, Gisbertz SS, Anderegg MCJ, Lagarde SM, Klaassen R, Meijer SL, van Dieren S, Hulshof M, Bergman J, Bennink RJ, van Laarhoven HWM, van Berge Henegouwen MI. 18F-FDG-PET/CT to Detect Pathological Complete Response After Neoadjuvant Treatment in Patients with Cancer of the Esophagus or Gastroesophageal Junction: Accuracy and Long-Term Implications. J Gastrointest Cancer 2024; 55:270-280. [PMID: 37393217 PMCID: PMC11096198 DOI: 10.1007/s12029-023-00951-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/09/2023] [Indexed: 07/03/2023]
Abstract
PURPOSE The curative strategy for patients with esophageal cancer without distant metastases consists of esophagectomy with preceding chemo(radio)therapy (CRT). In 10-40% of patients treated with CRT, no viable tumor is detectable in the resection specimen (pathological complete response (pCR)). This study aims to define the clinical outcomes of patients with a pCR and to assess the accuracy of post-CRT FDG-PET/CT in the detection of a pCR. METHODS Four hundred sixty-three patients with cancer of the esophagus or gastroesophageal junction who underwent esophageal resection after CRT between 1994 and 2013 were included. Patients were categorized as pathological complete responders or noncomplete responders. Standardized uptake value (SUV) ratios of 135 post-CRT FDG-PET/CTs were calculated and compared with the pathological findings in the corresponding resection specimens. RESULTS Of the 463 included patients, 85 (18.4%) patients had a pCR. During follow-up, 25 (29.4%) of these 85 patients developed recurrent disease. Both 5-year disease-free survival (5y-DFS) and 5-year overall survival (5y-OS) were significantly higher in complete responders compared to noncomplete responders (5y-DFS 69.6% vs. 44.2%; P = 0.001 and 5y-OS 66.5% vs. 43.7%; P = 0.001). Not pCR, but only pN0 was identified as an independent predictor of (disease-free) survival. CONCLUSION Patients with a pCR have a higher probability of survival compared to noncomplete responders. One third of patients with a pCR do develop recurrent disease, and pCR can therefore not be equated with cure. FDG-PET/CT was inaccurate to predict pCR and therefore cannot be used as a sole diagnostic tool to predict pCR after CRT for esophageal cancer.
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Affiliation(s)
- D C van der Aa
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
- Cancer Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands
| | - S S Gisbertz
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
- Cancer Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, Netherlands
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands
| | - M C J Anderegg
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
| | - S M Lagarde
- Department of Surgery, Erasmus Medical Center, Rotterdam, Netherlands
| | - R Klaassen
- Department of Medical Oncology, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
| | - S L Meijer
- Department of Pathology, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
| | - S van Dieren
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
| | - McCm Hulshof
- Department of Radiotherapy, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
| | - Jjghm Bergman
- Department of Gastroenterology, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
| | - R J Bennink
- Department of Radiology and Nuclear Medicine, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
| | - H W M van Laarhoven
- Cancer Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, Netherlands
- Department of Medical Oncology, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands
| | - M I van Berge Henegouwen
- Department of Surgery, Amsterdam UMC, location University of Amsterdam, Amsterdam, Netherlands.
- Cancer Treatment and Quality of Life, Cancer Center Amsterdam, Amsterdam, Netherlands.
- Amsterdam Gastroenterology Endocrinology Metabolism, Amsterdam, Netherlands.
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Sönmez RE, Besson FL, Ghidaglia J, Lewin M, Gomez L, Salloum C, Pittau G, Ciacio O, Allard MA, Cherqui D, Adam R, Sa Cunha A, Azoulay D, Vibert E, Golse N. Towards refining the utility of dual (18F-FDG / 18F-Choline) PET/CT for the management of hepatocellular carcinoma: a tertiary center study. THE QUARTERLY JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING : OFFICIAL PUBLICATION OF THE ITALIAN ASSOCIATION OF NUCLEAR MEDICINE (AIMN) [AND] THE INTERNATIONAL ASSOCIATION OF RADIOPHARMACOLOGY (IAR), [AND] SECTION OF THE SOCIETY OF... 2023; 67:206-214. [PMID: 36345856 DOI: 10.23736/s1824-4785.22.03485-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
BACKGROUND The role of positron emission tomography/computed tomography (PET/CT) in hepatocellular carcinoma (HCC) management is not clearly defined. Our objective was to analyze the utility of dual-PET/CT (18F-FDG + 18F-Choline) imaging findings on the BCLC staging and treatment decision for HCC patients. METHODS Between January 2011 and April 2019, 168 consecutive HCC patients with available baseline dual-PET/CT imaging data were retrospectively analyzed. To identify potential refinement criteria for surgically-treated patients, survival Kaplan-Meier curves of various standard-of-care and dual-PET/CT baseline parameters were estimated. Finally, multivariate cox proportional hazard ratios of the most relevant clinico-biological and/or PET parameters were estimated. RESULTS Dual-PET/CT findings increased the score of BCLC staging in 21 (12.5%) cases. In 24.4% (N.=41) of patients, the treatment strategy was modified by the PET findings. Combining AFP levels at a threshold of 10 ng/mL with 18F-FDG or 18F-Choline N status significantly impacted DFS (P<0.05). In particular, the combined criteria of the N+ status assessed by 18F-Choline with AFP threshold of 10 ng/mL provided a highly predictive composite parameter for estimation of DFS according to multivariate analysis (HR=10.6, P<0.05). CONCLUSIONS The 18F-Choline / AFP composite parameter appears promising, and further prospective studies are mandatory to validate its oncological impact.
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Affiliation(s)
- Recep Erçin Sönmez
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France -
| | - Florent L Besson
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Paris-Saclay University Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France
- Paris-Saclay University, CEA, CNRS, Inserm, BioMaps, Orsay, France
- School of Medicine, Paris-Saclay Univrsity, Le Kremlin-Bicêtre, France
| | - Jerome Ghidaglia
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Paris-Saclay University Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France
| | - Maïté Lewin
- Department of Radiology, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Centre Hépato-Biliaire, Villejuif, France
| | - Lea Gomez
- Department of Biophysics and Nuclear Medicine-Molecular Imaging, Paris-Saclay University Hospital, Assistance Publique-Hôpitaux de Paris, Le Kremlin-Bicêtre, France
| | - Chady Salloum
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
| | - Gabriella Pittau
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
| | - Oriana Ciacio
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
| | - Marc Antoine Allard
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
| | - Daniel Cherqui
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
| | - René Adam
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Research Group Chronotherapy, Cancers and Transplantation, Paris-Saclay University, Paris, France
| | - Antonio Sa Cunha
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
| | - Daniel Azoulay
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
| | - Eric Vibert
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
| | - Nicolas Golse
- Department of Hepatobiliary Surgery, Hepato-Biliary Center, Paul-Brousse Hospital, Assistance Publique Hôpitaux de Paris, Villejuif, France
- Department of Pathogenesis and Treatment of Liver Diseases, Paris-Saclay University, INSERM, UMR-S 1193, Paris, France
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7
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Veenstra EB, Ruiter SJS, de Haas RJ, de Jong KP, Erba PA, Dierckx RAJO, Noordzij W. A dual-tracer approach using [ 11C]CH and [ 18F]FDG in HCC clinical decision making. EJNMMI Res 2023; 13:77. [PMID: 37644167 PMCID: PMC10465408 DOI: 10.1186/s13550-023-01024-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 07/30/2023] [Indexed: 08/31/2023] Open
Abstract
BACKGROUND Early detection of recurrent or progressive HCC remains the strongest prognostic factor for survival. Dual tracer PET/CT imaging with [11C]CH and [18F]FDG can further increase detection rates as both tracers entail different metabolic pathways involved in HCC development. We investigated dual-tracer PET/CT in clinical decision making in patients suspected of recurrent or progressive HCC. All HCC patients who underwent both [11C]CH and [18F]FDG PET/CT in our institute from February 2018 to December 2021 were included. Both tracer PET/CT were within 4 weeks of each other with at least 6-month follow-up. Patients underwent dual tracer PET/CT because of unexplained and suspicious CT/MRI or sudden rise of serum tumour markers. A detected lesion was considered critical when the finding had prognostic consequences leading to treatment changes. RESULTS Nineteen patients who underwent [11C]CH and [18F]FDG PET/CT were included of which all but six patients were previously treated for HCC. Dual-tracer critical finding detection rate was 95%, with [18F]FDG 68%, and [11C]CH 84%. Intrahepatic HCC recurrence finding rate was 65% for both tracers. [18F]FDG found more ablation site recurrences (4/5) compared to [11C]CH (2/5). Only [11C]CH found two needle tract metastases. Both tracers found 75% of the positive lymph nodes. Two new primary tumours were found, one by [18F]FDG and both by [11C]CH. CONCLUSIONS Our study favours a dual-tracer approach in HCC staging in high-risk patients or when conventional imaging is non-conclusive.
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Affiliation(s)
- Emile B Veenstra
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
| | - Simeon J S Ruiter
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Robbert J de Haas
- Department of Radiology, Medical Imaging Center, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Koert P de Jong
- Department of Hepato-Pancreato-Biliary Surgery and Liver Transplantation, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - Paola A Erba
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands
- Department of Medicine and Surgery, Nuclear Medicine UnitASST - Ospedale Papa Giovanni, University of Milan-Bicocca, Piazza, Bergamo, Italy
| | - Rudi A J O Dierckx
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands
| | - Walter Noordzij
- Department of Nuclear Medicine and Molecular Imaging, Medical Imaging Center, University of Groningen, University Medical Center Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands
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8
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Nyakale N, Filippi L, Aldous C, Sathekge M. Update on PET Radiopharmaceuticals for Imaging Hepatocellular Carcinoma. Cancers (Basel) 2023; 15:cancers15071975. [PMID: 37046636 PMCID: PMC10093680 DOI: 10.3390/cancers15071975] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/12/2023] [Accepted: 03/21/2023] [Indexed: 03/29/2023] Open
Abstract
Numerous positron emission tomography (PET) targets for detection and staging of hepatocellular cancer have been developed in recent years. Hepatocellular carcinomas (HCCs) are clinically and pathologically heterogeneous tumours with a high tendency to be aggressive and unresponsive to chemotherapy. Early detection is essential, and the need for an adequate imaging biomarker, which can overcome some of the limitations of conventional radiological imaging, is persistent. Flourine-18 (18F) flourodeoxyglucose (FDG), the most widely used PET radiopharmaceutical, has proven disappointing as a possible staple in the evaluation of HCC. This disappointment had led to experimentation with carious radiotracers, such as the choline derivatives, acetate, and prostate-specific membrane antigen, which appear to complement and/or enhance the role of FDG. In this study, we look at the various PET radiopharmaceuticals that have been used for imaging HCC and the particular pathways that they target in HCC and liver cancers.
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9
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Chen H, Teng M, Zhang H, Liang X, Cheng H, Liu G. Advanced radionuclides in diagnosis and therapy for hepatocellular carcinoma. CHINESE CHEM LETT 2022; 33:3371-3383. [DOI: 10.1016/j.cclet.2022.03.079] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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10
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Wang R, Quan Z, Zheng T, Wang K, Liu Y, Han Z, Wang X, Ma S, Liu L, Lau WY, Sun X. Pathophysiological mechanisms of ALPPS: experimental model. Br J Surg 2022; 109:510-519. [PMID: 35576390 DOI: 10.1093/bjs/znac007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2021] [Revised: 01/05/2022] [Accepted: 01/05/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) is a two-stage strategy that may increase hepatic tumour resectability and reduce postoperative liver failure rate by inducing rapid hypertrophy of the future liver remnant (FLR). Pathophysiological mechanisms after the first stage of ALPPS are poorly understood. METHODS An ALPPS model was established in rabbits with liver VX2 tumour. The pathophysiological mechanisms after the first stage of ALPPS in the FLR and tumour were assessed by multiplexed positron emission tomography (PET) tracers, dynamic contrast-enhanced MRI (DCE-MRI) and histopathology. RESULTS Tumour volume in the ALPPS model differed from post-stage 1 ALPPS at day 14 compared to control animals. 18F-FDG uptake of tumour increased from day 7 onwards in the ALPPS model. Valid volumetric function measured by 18F-methylcholine PET showed good values in accurately monitoring dynamics and time window for functional liver regeneration (days 3 to 7). DCE-MRI revealed changes in the vascular hyperpermeability function, with a peak on day 7 for tumour and FLR. CONCLUSION Molecular and functional imaging are promising non-invasive methods to investigate the pathophysiological mechanisms of ALPPS with potential for clinical application.
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Affiliation(s)
- Ruifeng Wang
- NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang, China
- Department of Nuclear Medicine, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China
- Department of Gastroenterology, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China
| | - Zhen Quan
- NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang, China
- Department of Nuclear Medicine, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China
| | - Tongsen Zheng
- Department of Gastrointestinal Medical Oncology, The Affiliated Tumour Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, China
| | - Kai Wang
- NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang, China
- Department of Nuclear Medicine, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China
| | - Yang Liu
- NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang, China
- Department of Nuclear Medicine, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China
| | - Zhaoguo Han
- NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang, China
- Department of Nuclear Medicine, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China
- Biomedical Research Imaging Center, Department of Radiology, and UNC Lineberger Comprehensive Cancer Center, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina, USA
| | - Xiance Wang
- NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang, China
- Department of Nuclear Medicine, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China
| | - Shiling Ma
- NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang, China
- Department of Nuclear Medicine, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China
| | - Lianxin Liu
- Department of Hepatic Surgery, The First Affiliated Hospital of Harbin Medical University, Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Harbin, Heilongjiang Province 150001, China
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, China
| | - Wan Yee Lau
- Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR 999077, China
| | - Xilin Sun
- NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics, Molecular Imaging Research Center (MIRC), Harbin Medical University, Harbin, Heilongjiang, China
- Department of Nuclear Medicine, The Fourth Hospital of Harbin Medical University, Harbin, Heilongjiang 150028, China
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11
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Abouzied MM, Alhinti N, AlMuhaideb A, Al Sugair AS, Al Qahtani M. Extrahepatic metastases from hepatocellular carcinoma: multimodality image evaluation. Nucl Med Commun 2021; 42:583-591. [PMID: 33625188 DOI: 10.1097/mnm.0000000000001380] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
The most prevalent primary malignancy of the liver is hepatocellular carcinoma (HCC); its poor prognosis is mainly related to intrahepatic recurrence and extrahepatic metastases. However, survival from HCC has improved due to better control of the primary tumor, the development of newer treatment modalities, including liver transplant, together with advances in imaging techniques. Therefore, the significance of patient management as corresponds with distant metastases has increased; since the proper evaluation and detection of extrahepatic metastases is crucial to optimize potential therapy for patients. Conventional imaging like CT, MRI play crucial rule in patient's diagnosis and qualifying for a certain type of therapy. More recently, a molecular imaging tool with radiolabeled deoxyglucose and fluorocholine has proved its promising value as a complementary tool to conventional studies. In this review, the frequent sites of metastases and HCC spread are discussed as well as the imaging findings as seen by both conventional imaging techniques and by molecular imaging tools, namely 18F-Choline PET/CT, and FDG PET. The implications of guiding treatment planning have also been discussed.
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Affiliation(s)
| | - Nayef Alhinti
- Department of Radiology, King Faisal Specialist Hospital & Research Centre
| | - Ahmad AlMuhaideb
- Department of Radiology, King Faisal Specialist Hospital & Research Centre
| | | | - Mohammed Al Qahtani
- Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
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12
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Aujay G, Debordeaux F, Blanc JF, Lapuyade B, Papadopoulos P, Bordenave L, Trillaud H, Pinaquy JB. 18F-choline PET-computed tomography for the prediction of early treatment responses to transarterial radioembolization in patients with hepatocellular carcinoma. Nucl Med Commun 2021; 42:633-638. [PMID: 33660694 DOI: 10.1097/mnm.0000000000001383] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Transarterial radioembolization (TARE) is widely used for the treatment of hepatocellular carcinoma (HCC), but early treatment response can be very difficult to assess. The aim was to evaluate 18F-fluorocholine PET/computed tomography (CT) to assess the treatment response in patients with intermediate or locally advanced HCC. METHODS Between March 2019 and July 2020, nine HCC patients treated with TARE, who underwent PET/CT at baseline and 1 month after treatment, were enrolled. The maximum, mean (SUVmean), and peak (SUVpeak) standardized uptake value (SUV), SUV normalized by lean body mass (SUL), and total lesion glycolysis (TLG) were measured. Statistical analysis used the Mann-Whitney test to evaluate the differences in parameters between responders (partial and complete response) and nonresponders (stable or progressive disease) at the 6-month follow-up, according to the modified Response Evaluation Criteria in Solid Tumors. RESULTS Three patients were nonresponders (progressive disease and stable disease) and six were responders. Delta SUVmean, delta SUL, and delta TLG could predict an early response (P = 0.02, P = 0.04, and P = 0.02, respectively). None of the pre-therapeutic parameters were correlated with the response. Post-therapeutic SUL, SUVmean, TLG, and SUVpeak were also predictive of the response. CONCLUSIONS Our preliminary results showed that changes in certain metabolic parameters (from baseline PET to 1-month PET) are predictive of the response to TARE in HCC (Delta SUVmean, delta TLG, and delta SUL). The absence of post-treatment inflammation could lead to a better prediction than MRI evaluation. This study suggests that 1-month 18F-choline PET/CT could modify the clinical management predicting responders.Video Abstract: http://links.lww.com/NMC/A193.
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13
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Abouzied MM, Fathala A, AlMuhaideb A, Almanea H, Al-Sugair AS, AlSkaff R, Al-Qahtani MH. Gastric wall metastases from hepatocellular carcinoma: case report and review of the literature. Radiol Case Rep 2021; 16:550-554. [PMID: 33384755 PMCID: PMC7770481 DOI: 10.1016/j.radcr.2020.12.047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2020] [Revised: 12/16/2020] [Accepted: 12/16/2020] [Indexed: 01/10/2023] Open
Abstract
A 69-year-old male patient who had a history of well-differentiated hepatocellular carcinoma (HCC) post right hepatectomy presented a year later with iron-deficiency anemia. His anemia work-up included upper endoscopy that revealed multiple gastric polyp a biopsy from the largest demonstrated metastatic hepatocellular carcinoma. His magnetic resonance imaging (MRI) showed a gastric "polyp" without evidence of local HCC recurrence within the liver. His subsequent dual imaging with Choline/fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) confirmed the gastric metastases and in addition revealed other sites of unexpected metastatic disease in the right adrenal and the bone that was asymptomatic. Patient was started on sorafenib and currently he is alive one-and-half-year postdetection of his metastatic disease under palliative care. This case showed that the possibility of gastric metastases should be kept in mind when confronted with anemia in HCC patient and also highlight the complementary role of molecular imaging modality along with MRI in the metastatic work-up for hepatocellular carcinoma postcurative resection.
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Affiliation(s)
- Moheieldin M Abouzied
- Department of Radiology, Medical Imaging Service, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Ahmed Fathala
- Department of Radiology, Medical Imaging Service, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Ahmad AlMuhaideb
- Department of Radiology, Medical Imaging Service, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Hadeel Almanea
- Pathology and Laboratory Medicine Department, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Abdulaziz S Al-Sugair
- Department of Radiology, Medical Imaging Service, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Rasha AlSkaff
- Department of Radiology, Medical Imaging Service, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia
| | - Mohammed H Al-Qahtani
- Cyclotron and Radiopharmaceuticals Department, King Faisal Specialist Hospital and Research Centre, MBC#28, P.O. Box 3354, Riyadh 11211, Saudi Arabia
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14
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Sharma R, Inglese M, Dubash S, Lu H, Pinato DJ, Sanghera C, Patel N, Chung A, Tait PD, Mauri F, Crum WR, Barwick TD, Aboagye EO. Monitoring Response to Transarterial Chemoembolization in Hepatocellular Carcinoma Using 18F-Fluorothymidine PET. J Nucl Med 2020; 61:1743-1748. [PMID: 32513905 PMCID: PMC8679631 DOI: 10.2967/jnumed.119.240598] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Accepted: 04/03/2020] [Indexed: 12/21/2022] Open
Abstract
Accurate disease monitoring is essential after transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) because of the potential for profound adverse events and large variations in survival outcome. Posttreatment changes on conventional imaging can confound determination of residual or recurrent disease, magnifying the clinical challenge. On the basis of increased expression of thymidylate synthase (TYMS), thymidine kinase 1 (TK-1), and equilibrative nucleoside transporter 1 (SLC29A1) in HCC compared with liver tissue, we conducted a proof-of-concept study evaluating the efficacy of 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) PET to assess response to TACE. Because previous PET studies in HCC have been hampered by high background liver signal, we investigated whether a temporal-intensity voxel clustering (kinetic spatial filtering, or KSF) improved lesion detection. Methods: A tissue microarray was built from 36 HCC samples and from matching surrounding cirrhotic tissue and was stained for TK-1 A prospective study was conducted; 18 patients with a diagnosis of HCC by the criteria of the American Association for the Study of Liver Diseases who were eligible for treatment with TACE were enrolled. The patients underwent baseline conventional imaging and dynamic 18F-FLT PET with KSF followed by TACE. Imaging was repeated 6-8 wk after TACE. The PET parameters were compared with modified enhancement-based RECIST. Results: Cancer Genome Atlas analysis revealed increased RNA expression of TYMS, TK-1, and SLC29A1 in HCC. TK-1 protein expression was significantly higher in HCC (P < 0.05). The sensitivity of 18F-FLT PET for baseline HCC detection was 73% (SUVmax, 9.7 ± 3.0; tumor to liver ratio, 1.2 ± 0.3). Application of KSF did not improve lesion detection. Lesion response after TACE by modified RECIST was 58% (14 patients with 24 lesions). A 30% reduction in mean 18F-FLT PET uptake was observed after TACE, correlating with an observed PET response of 60% (15/25). A significant and profound reduction in the radiotracer delivery parameter K1 after TACE was observed. Conclusion:18F-FLT PET can differentiate HCC from surrounding cirrhotic tissue, with PET parameters correlating with TACE response. KSF did not improve visualization of tumor lesions. These findings warrant further investigation.
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Affiliation(s)
- Rohini Sharma
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - Marianna Inglese
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - Suraiya Dubash
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - Haonan Lu
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - David J Pinato
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - Chandan Sanghera
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - Neva Patel
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
- Radiological Sciences Unit, Imperial College Healthcare NHS Trust, London, United Kingdom
| | - Anthony Chung
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - Paul D Tait
- Department of Radiology, Imperial College Healthcare NHS Trust, London, United Kingdom; and
| | - Francesco Mauri
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
| | - William R Crum
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
- Institute of Translational Medicine and Therapeutics, Imperial College London, London, United Kingdom
| | - Tara D Barwick
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
- Department of Radiology, Imperial College Healthcare NHS Trust, London, United Kingdom; and
| | - Eric O Aboagye
- Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital, London, United Kingdom
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15
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Bialek E, Dziuk M, Witkowska-Patena E, Kwasiborski P, Piszczek S. Adrenal glands uptake patterns in 18F-Fluoroethylcholine PET/CT. Rev Esp Med Nucl Imagen Mol 2020. [DOI: 10.1016/j.remnie.2019.10.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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16
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Bialek E, Dziuk M, Witkowska-Patena E, Kwasiborski P, Piszczek S. Patrones de captación en las glándulas suprarrenales de la PET/TC con 18F-Fluoroetilcolina. Rev Esp Med Nucl Imagen Mol 2020; 39:84-91. [DOI: 10.1016/j.remn.2019.09.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2019] [Revised: 09/06/2019] [Accepted: 09/10/2019] [Indexed: 11/28/2022]
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17
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Wallace MC, Sek K, Francis RJ, Samuelson S, Ferguson J, Tibballs J, Asad A, Preen DB, MacQuillan G, Garas G, Adams LA, Jeffrey GP. Baseline and Post-treatment 18F-Fluorocholine PET/CT Predicts Outcomes in Hepatocellular Carcinoma Following Locoregional Therapy. Dig Dis Sci 2020; 65:647-657. [PMID: 31440998 DOI: 10.1007/s10620-019-05781-6] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2019] [Accepted: 08/07/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS 18F-fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) is an emerging functional imaging technique in the diagnosis and management of hepatocellular carcinoma (HCC). The aim of this study was to assess the ability of a pre- and post-treatment 18F-FCH PET/CT to predict prognosis and treatment response in early-stage HCC. METHODS Patients with early- or intermediate-stage HCC planned for locoregional therapy were prospectively enrolled. Baseline demographic and tumor information was collected and baseline and post-treatment 18F-FCH PET/CT performed. Maximum standardized uptake values (SUVmax) were determined for each HCC lesion, and the difference between baseline and post-treatment SUVmax values were compared with progression-free survival outcomes. RESULTS A total of 29 patients with 39 confirmed HCC lesions were enrolled from a single clinical center. Patients were mostly men (89.7%) with hepatitis C or alcohol-related cirrhosis (65.5%) and early-stage disease (89.7%). Per-patient and per-lesion sensitivity of 18F-FCH PET/CT was 72.4% and 59.0%, respectively. A baseline SUVmax < 13 was associated with a superior median progression-free survival compared with an SUVmax of > 13 (17.7 vs. 5.1 months; p = 0.006). A > 45% decrease in SUVmax between baseline and post-treatment 18F-FCH PET/CT ("responders") was associated with a superior mean progression-free survival than a percentage decrease of < 45% ("non-responders," 36.1 vs. 11.6 months; p = 0.034). CONCLUSIONS Baseline and post-treatment 18F-FCH PET/CT predicts outcomes in early-stage HCC undergoing locoregional therapy. This technique may identify patients with an objective response post-locoregional therapy who would benefit from further therapy.
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Affiliation(s)
- Michael C Wallace
- Department of Hepatology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Perth, 6009, WA, Australia. .,Medical School, University of Western Australia, Nedlands, WA, Australia. .,School of Population and Global Health, University of Western Australia, Nedlands, WA, Australia.
| | - Kenny Sek
- Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Roslyn J Francis
- Medical School, University of Western Australia, Nedlands, WA, Australia.,Department of Nuclear Medicine, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Shaun Samuelson
- Department of Radiology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - John Ferguson
- Department of Radiology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Jonathan Tibballs
- Department of Radiology, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - Ali Asad
- Department of Medical Technology and Physics, Sir Charles Gairdner Hospital, Nedlands, WA, Australia
| | - David B Preen
- School of Population and Global Health, University of Western Australia, Nedlands, WA, Australia
| | - Gerry MacQuillan
- Department of Hepatology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Perth, 6009, WA, Australia.,Medical School, University of Western Australia, Nedlands, WA, Australia
| | - George Garas
- Department of Hepatology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Perth, 6009, WA, Australia.,Medical School, University of Western Australia, Nedlands, WA, Australia
| | - Leon A Adams
- Department of Hepatology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Perth, 6009, WA, Australia.,Medical School, University of Western Australia, Nedlands, WA, Australia
| | - Gary P Jeffrey
- Department of Hepatology, Sir Charles Gairdner Hospital, Hospital Avenue, Nedlands, Perth, 6009, WA, Australia.,Medical School, University of Western Australia, Nedlands, WA, Australia
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Hypoxia-induced modulation of glucose transporter expression impacts 18F-fluorodeoxyglucose PET-CT imaging in hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2019; 47:787-797. [PMID: 31832727 DOI: 10.1007/s00259-019-04638-4] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2019] [Accepted: 11/22/2019] [Indexed: 12/24/2022]
Abstract
PURPOSE To investigate the molecular mechanisms underlying the variable standard uptake value (SUV) of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) imaging in hepatocellular carcinoma (HCC) and whether hypoxia-induced glucose transporter expression contributes to the progression of HCC and the rate of glycolysis in HCC cells. MATERIALS AND METHODS Sixteen HCC specimens obtained from patients who underwent pre-treatment staging with 18F-FDG PET-CT imaging were divided into high maximum SUV (SUVmax > 8) and low SUVmax (SUVmax < 5) groups and employed for whole-genome gene expression profiling using GeneChip Human Genome U133 Plus 2.0 Arrays. The relationship between SUVmax and the expression of glucose transporters 1 and 3 (GLUT1 and GLUT3) was further validated using immunohistochemical analysis. The expression of GLUT1 and GLUT3 in different HCC cells under hypoxia and normoxia conditions were monitored by quantitative reverse transcription PCR (RT-qPCR). Glycolysis and FDG uptake by HCC cells were measured using the Seahorse XF glycolysis stress test and 18F-FDG PET-CT imaging. The effect of GLUT1 and GLUT3 on glucose uptake in HCC cells was examined using the fluorescent D-glucose analog 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxy-d-glucose (2-NBDG) followed by detection of fluorescence produced by the cells using flow cytometry. RESULTS Glucose transporters are differentially expressed between samples from HCC patients with high and low SUVmax. In particular, over-expression of GLUT1 and GLUT3 in high SUVmax patients was correlated with high glucose uptake and overall survival. The expression of GLUT1 and GLUT3 was significantly induced by hypoxia in different HCC cells. High expression of GLUT1 and GLUT3 in HCC cells were correlated with high rates of glycolysis and 18F-FDG uptake. Therefore, our data suggested that hypoxia-induced glucose transporters expression could result in the variations of 18F-FDG PET-CT imaging and progression of HCC, contributing to more aggressive disease phenotypes like large tumor size, recurrence, and poor survival. CONCLUSION Over-expression of GLUT1 and GLUT3 significantly increase glucose uptake in HCC cells. Hypoxia-induced glucose transporters expression may therefore be a contributing variable in 18F-FDG PET-CT imaging and progression in HCC.
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Wang G, Zhao W, Wang H, Qiu G, Jiang Z, Wei G, Li X. Exosomal MiR-744 Inhibits Proliferation and Sorafenib Chemoresistance in Hepatocellular Carcinoma by Targeting PAX2. Med Sci Monit 2019; 25:7209-7217. [PMID: 31553714 PMCID: PMC6777417 DOI: 10.12659/msm.919219] [Citation(s) in RCA: 70] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a commonly occurring liver malignancy. Its prognosis remains unsatisfactory. Accumulating evidence has revealed that exosomal microRNAs (miRNAs) act as biomarkers and play crucial roles in the advancement of HCC. The current study explored the biological role and fundamental mechanism of exosomal miR-744 in HCC. MATERIAL AND METHODS The serum exosomes of HCC patients were isolated by differential ultracentrifugation. MiR-744 expression in HCC tissues, cell lines and serum exosomes were detected by quantitative real-time polymerase chain reaction (qRT-PCR). EdU (5-ethynyl-2'-deoxyuridine) assay and Cell Counting Kit-8 (CCK-8) assay were conducted to show the impacts of miR-744 or exosomal miR-744 on proliferation and sorafenib resistance in HepG2 cells. The target of miR-744 was ascertained by regulating the level of miR-744 in HepG2 cells. RESULTS MiR-744 is downregulated in HCC tissues and cell lines as well as in exosomes derived from patient serum and HepG2 cells. Additionally, downregulated miR-744 promotes HepG2 cell proliferation and inhibits the chemosensitivity of HepG2 cells to sorafenib. PAX2 was identified as the functional target of miR-744. Interestingly, miR-744 is decreased in exosomes derived from sorafenib-resistant HepG2 cells. Furthermore, when treated with the miR-744-enriched exosomes, the proliferation of HepG2 cells was significantly suppressed, and the sorafenib resistance was reduced. CONCLUSIONS MiR-744 has an imperative role in the propagation and chemoresistance of HCC. Serum exosomal miR-744 might act as a biomarker of HCC, and exosomal miR-744 might offer an innovative strategy for HCC treatment.
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Affiliation(s)
- Guanghui Wang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Wei Zhao
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Huxia Wang
- Department of Breast Surgery, Shaanxi Provincial Tumor Hospital, Xi'an, Shaanxi, China (mainland)
| | - Guanglin Qiu
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Zhengdong Jiang
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Guangbing Wei
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
| | - Xuqi Li
- Department of General Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China (mainland)
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Gougelet A, Sartor C, Senni N, Calderaro J, Fartoux L, Lequoy M, Wendum D, Talbot JN, Prignon A, Chalaye J, Imbeaud S, Zucman-Rossi J, Tordjmann T, Godard C, Bossard P, Rosmorduc O, Amaddeo G, Colnot S. Hepatocellular Carcinomas With Mutational Activation of Beta-Catenin Require Choline and Can Be Detected by Positron Emission Tomography. Gastroenterology 2019; 157:807-822. [PMID: 31194980 DOI: 10.1053/j.gastro.2019.05.069] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/23/2018] [Revised: 05/18/2019] [Accepted: 05/28/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS In one-third of hepatocellular carcinomas (HCCs), cancer cells have mutations that activate β-catenin pathway. These cells have alterations in glutamine, bile, and lipid metabolism. We investigated whether positron emission tomography (PET) imaging allows identification of altered metabolic pathways that might be targeted therapeutically. METHODS We studied mice with activation of β-catenin in liver (Apcko-liv mice) and male C57Bl/6 mice given injections of diethylnitrosamine, which each develop HCCs. Mice were fed a conventional or a methionine- and choline-deficient diet or a choline-deficient (CD) diet. Choline uptake and metabolism in HCCs were analyzed by micro-PET imaging of mice; livers were collected and analyzed by histologic, metabolomic, messenger RNA quantification, and RNA-sequencing analyses. Fifty-two patients with HCC underwent PET imaging with 18F-fluorodeoxyglucose, followed by 18F-fluorocholine tracer metabolites. Human HCC specimens were analyzed by immunohistochemistry, quantitative polymerase chain reaction, and DNA sequencing. We used hepatocytes and mouse tumor explants for studies of incorporation of radiolabeled choline into phospholipids and its contribution to DNA methylation. We analyzed HCC progression in mice fed a CD diet. RESULTS Livers and tumors from Apcko-liv mice had increased uptake of dietary choline, which contributes to phospholipid formation and DNA methylation in hepatocytes. In patients and in mice, HCCs with activated β-catenin were positive in 18F-fluorocholine PET, but not 18F-fluorodeoxyglucose PET, and they overexpressed the choline transporter organic cation transporter 3. The HCC cells from Apcko-liv mice incorporated radiolabeled methyl groups of choline into phospholipids and DNA. In Apcko-liv mice, the methionine- and choline-deficient diet reduced proliferation and DNA hypermethylation of hepatocytes and HCC cells, and the CD diet reduced long-term progression of tumors. CONCLUSIONS In mice and humans, HCCs with mutations that activate β-catenin are characterized by increased uptake of a fluorocholine tracer, but not 18F-fluorodeoxyglucose, revealed by PET. The increased uptake of choline by HCCs promotes phospholipid formation, DNA hypermethylation, and hepatocyte proliferation. In mice, the CD diet reverses these effects and promotes regression of HCCs that overexpress β-catenin.
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Affiliation(s)
- Angélique Gougelet
- Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique, Unité Mixte De Recherché 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale Unité Mixte De Recherche 1138, Equipe Labellisée Ligue Contre le Cancer, Paris, France
| | - Chiara Sartor
- Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique, Unité Mixte De Recherché 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Nadia Senni
- Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique, Unité Mixte De Recherché 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France
| | - Julien Calderaro
- Assistance Publique-Hôpitaux de Paris, Département de Pathologie, Hôpital Universitaire Henri Mondor, Créteil, France; Institut National de la Santé et de la Recherche Médicale U955, Team 18, Institut Mondor de Recherche Biomédicale; Université Paris Est Créteil, Créteil, France
| | - Laetitia Fartoux
- Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, Hôpital St-Antoine, Sorbonne Université, Paris, France; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Saint-Antoine, Paris, France
| | - Marie Lequoy
- Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, Hôpital St-Antoine, Sorbonne Université, Paris, France; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Saint-Antoine, Paris, France
| | - Dominique Wendum
- Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Saint-Antoine, Paris, France; Assistance Publique-Hôpitaux de Paris, Anatomie Pathologique, Hôpital St-Antoine, Sorbonne Université, Paris, France
| | - Jean-Noël Talbot
- Assistance Publique-Hôpitaux de Paris, Médecine Nucléaire, Hôpital Tenon, Sorbonne Université, Paris, France; Laboratoire d'Imagerie Moléculaire Photonique, UMS28, Phénotypage du Petit Animal, Sorbonne Université, Paris, France
| | - Aurélie Prignon
- Laboratoire d'Imagerie Moléculaire Photonique, UMS28, Phénotypage du Petit Animal, Sorbonne Université, Paris, France
| | - Julia Chalaye
- Assistance Publique-Hôpitaux de Paris, Médecine Nucléaire, Hôpital Universitaire Henri Mondor, Créteil, France
| | - Sandrine Imbeaud
- Institut National de la Santé et de la Recherche Médicale, Unité Mixte De Recherché 1162, Génomique Fonctionnelle des Tumeurs Solides, Equipe Labellisée Ligue Contre le Cancer, Institut Universitaire d'Hematologie, Paris, France
| | - Jessica Zucman-Rossi
- Institut National de la Santé et de la Recherche Médicale, Unité Mixte De Recherché 1162, Génomique Fonctionnelle des Tumeurs Solides, Equipe Labellisée Ligue Contre le Cancer, Institut Universitaire d'Hematologie, Paris, France
| | - Thierry Tordjmann
- Institut National de la Santé et de la Recherche Médicale U1174, Université Paris Sud, Orsay, France
| | - Cécile Godard
- Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique, Unité Mixte De Recherché 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale Unité Mixte De Recherche 1138, Equipe Labellisée Ligue Contre le Cancer, Paris, France
| | - Pascale Bossard
- Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique, Unité Mixte De Recherché 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale Unité Mixte De Recherche 1138, Equipe Labellisée Ligue Contre le Cancer, Paris, France
| | - Olivier Rosmorduc
- Assistance Publique-Hôpitaux de Paris, Service d'Hépatologie, Hôpital St-Antoine, Sorbonne Université, Paris, France; Sorbonne Université, Institut National de la Santé et de la Recherche Médicale, Centre de Recherche Saint-Antoine, Paris, France
| | - Giuliana Amaddeo
- Assistance Publique-Hôpitaux de Paris, Médecine Interne, Hôpital Universitaire Henri Mondor, Créteil, France
| | - Sabine Colnot
- Institut Cochin, Institut National de la Santé et de la Recherche Médicale U1016, Centre National de la Recherche Scientifique, Unité Mixte De Recherché 8104, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Centre de Recherche des Cordeliers, Institut National de la Santé et de la Recherche Médicale Unité Mixte De Recherche 1138, Equipe Labellisée Ligue Contre le Cancer, Paris, France.
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Lu RC, She B, Gao WT, Ji YH, Xu DD, Wang QS, Wang SB. Positron-emission tomography for hepatocellular carcinoma: Current status and future prospects. World J Gastroenterol 2019; 25:4682-4695. [PMID: 31528094 PMCID: PMC6718031 DOI: 10.3748/wjg.v25.i32.4682] [Citation(s) in RCA: 53] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Revised: 06/30/2019] [Accepted: 07/19/2019] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer mortality worldwide. Various imaging modalities provide important information about HCC for its clinical management. Since positron-emission tomography (PET) or PET-computed tomography was introduced to the oncologic setting, it has played crucial roles in detecting, distinguishing, accurately staging, and evaluating local, residual, and recurrent HCC. PET imaging visualizes tissue metabolic information that is closely associated with treatment. Dynamic PET imaging and dual-tracer have emerged as complementary techniques that aid in various aspects of HCC diagnosis. The advent of new radiotracers and the development of immuno-PET and PET-magnetic resonance imaging have improved the ability to detect lesions and have made great progress in treatment surveillance. The current PET diagnostic capabilities for HCC and the supplementary techniques are reviewed herein.
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Affiliation(s)
- Ren-Cai Lu
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Bo She
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Wen-Tao Gao
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Yun-Hai Ji
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Dong-Dong Xu
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Quan-Shi Wang
- Nanfang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
| | - Shao-Bo Wang
- PET-CT Center, the First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
- Yunnan Key Laboratory of Primate Biomedical Research, Institute of Primate Translational Medicine, Kunming University of Science and Technology, Kunming 650093, Yunnan Province, China
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Detection rate of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: an updated systematic review and meta-analysis. Clin Transl Imaging 2019. [DOI: 10.1007/s40336-019-00332-5] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Positron emission tomography/computed tomography with 18F-fluorocholine improve tumor staging and treatment allocation in patients with hepatocellular carcinoma. J Hepatol 2018. [PMID: 29518452 DOI: 10.1016/j.jhep.2018.02.018] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND & AIMS Hepatocellular carcinoma (HCC) staging according to the Barcelona Clinical Liver Cancer (BCLC) classification is based on conventional imaging. The aim of our study was to assess the impact of dual-tracer 18F-fluorocholine and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) on tumor staging and treatment allocation. METHODS A total of 192 dual-tracer PET/CT scans (18F-fluorocholine and 18F-fluorodeoxyglucose PET/CT) were performed in 177 patients with HCC. BCLC staging and treatment proposal were retrospectively collected based on conventional imaging, along with any new lesions detected, and changes in BCLC classification or treatment allocation based on dual-tracer PET/CT. RESULTS Patients were primarily men (87.5%) with cirrhosis (71%) due to alcohol ± non-alcoholic steatohepatitis (26%), viral infection (62%) or unknown causes (12%). Among 122 patients with PET/CT performed for staging, BCLC stage based on conventional imaging was 0/A in 61 patients (50%), B in 32 patients (26%) and C in 29 patients (24%). Dual-tracer PET/CT detected new lesions in 26 patients (21%), upgraded BCLC staging in 14 (11%) and modified treatment strategy in 17 (14%). In addition, dual-tracer PET/CT modified the final treatment in 4/9 (44%) patients with unexplained elevation of alpha-fetoprotein (AFP), 10/25 patients (40%) with doubtful lesions on conventional imaging and 3/36 patients (8%) waiting for liver transplantation without active HCC after tumor response following bridging therapy. CONCLUSION When used for HCC staging, dual-tracer PET/CT enabled BCLC upgrading and treatment modification in 11% and 14% of patients, respectively. Dual-tracer PET/CT might also be useful in specific situations (an unexplained rise in AFP, doubtful lesions or pre-transplant evaluation of patients without active HCC). LAY SUMMARY Using a combination of tracers 18F-fluorocholine and 18F-fluorodeoxyglucose when performing positron emission tomography/computed tomography (PET/CT), often called a PET scan, helps to identify new tumor lesions in patients with hepatocellular carcinoma. This technique enabled staging modification of patients' tumors and led to changes in treatment allocation in certain patients.
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Combined [18F]-Fluoroethylcholine PET/CT and 99mTc-Macroaggregated Albumin SPECT/CT Predict Survival in Patients With Intermediate-Stage Hepatocellular Carcinoma. Clin Nucl Med 2018; 43:477-481. [PMID: 29659390 DOI: 10.1097/rlu.0000000000002092] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
AIM The aim of this study was to retrospectively analyze the prognostic value of combined Tc-macroaggregated albumin (MAA) SPECT/CT and [F]-fluoroethylcholine (FEC) PET/CT before radioembolization for survival of patients with intermediate-stage hepatocellular carcinoma. METHODS Twenty-four patients with known hepatocellular carcinoma Barcelona Clinic Liver Cancer stage B were eligible for this analysis. All patients were scheduled for radioembolization and received a pretherapeutic [F]FEC PET/CT scan as well as Tc-MAA SPECT/CT for hepatopulmonary shunting. Laboratory and semiquantitative PET parameters and morphologic and metabolic (intersection) volumes of MAA and FEC were evaluated. Spearman correlation with overall survival, receiver operating curve analyses, univariate and multivariate Cox regression, and Kaplan-Meier-analysis was applied. RESULTS All patients (5 female/19 male) are deceased within the observational period. Median survival was 395 days (±51 days; range, 23-1122 days). The percentage of hypervascularized metabolically active tumor volume (vascularized tumor ratio; defined as high MAA and FEC uptake) correlated significantly with survival. Vascularized tumor ratio was a significant predictor in univariate and multivariate analyses (P = 0.026; hazard ratio, 11.65; 95% confidence interval, 1.62-83.73; P = 0.015). Statistical significance was not reached by all other variables in multivariate analysis. Receiver operating curve analysis for 1-year survival revealed an area under the curve of 0.77 (P = 0.024) for vascularized tumor ratio. At a cutoff value of 9%, sensitivity, specificity, and positive and negative prediction were 83%, 67%, and 71% and 80% (P = 0.036). Patients with a higher tumor vascularization had a median survival of 274 ± 80 versus 585 ± 284 days (P = 0.015). CONCLUSIONS Hepatocellular carcinoma with high vascularization in metabolic active areas as assessed by combined FEC PET/CT and Tc-MAA SPECT/CT represents an unfavorable subgroup with reduced overall survival after radioembolization.
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Construction and Evaluation of the Tumor-Targeting, Cell-Penetrating Multifunctional Molecular Probe iCREKA. CONTRAST MEDIA & MOLECULAR IMAGING 2018; 2018:7929617. [PMID: 29686590 PMCID: PMC5857341 DOI: 10.1155/2018/7929617] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/11/2017] [Revised: 12/24/2017] [Accepted: 02/05/2018] [Indexed: 11/27/2022]
Abstract
A novel tumor stroma targeting and membrane-penetrating cyclic peptide, named iCREKA, was designed and labeled by fluorescein isothiocyanate (FITC) and positron emitter 18F to build the tumor-targeting tracers. The FITC-iCREKA was proved to have significantly higher cellular uptake in the glioma U87 cells in the presence of activated MMP-2 than that in absence of activated MMP-2 by cells fluorescence test in vitro. The tumor tissue fluorescence microscope imaging demonstrated that FITC-iCREKA accumulated in the walls of the blood vessels and the surrounding stroma in the glioma tumor at 1 h after intravenous injection. While at 3 h after injection, FITC-iCREKA was found to be uptaken in the tumor cells. However, the control FITC-CREKA can only be found in the tumor stroma, not in the tumor cells, no matter at 1 h or 3 h after injection. The whole-animal fluorescence imaging showed that the glioma tumor could be visualized clearly with high fluorescence signal. The microPET/CT imaging further demonstrated that 18F-iCREKA could target U87MG tumor in vivo from 30 min to 2 h after injection. The present study indicated the iCREKA had the capacity of tumor stroma targeting and the membrane-penetrating. It was potential to be developed as the fluorescent and PET tracers for tumor imaging.
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Ayuso C, Rimola J, Vilana R, Burrel M, Darnell A, García-Criado Á, Bianchi L, Belmonte E, Caparroz C, Barrufet M, Bruix J, Brú C. Diagnosis and staging of hepatocellular carcinoma (HCC): current guidelines. Eur J Radiol 2018; 101:72-81. [PMID: 29571804 DOI: 10.1016/j.ejrad.2018.01.025] [Citation(s) in RCA: 240] [Impact Index Per Article: 34.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2017] [Revised: 01/10/2018] [Accepted: 01/27/2018] [Indexed: 12/20/2022]
Abstract
One of the key strategies to improve the prognosis of HCC, beside prevention, is to diagnose the tumor in early stages, when the patient is asymptomatic and the liver function is preserved, because in this clinical situation effective therapies with survival benefit can be applied. Imaging techniques are a key tool in the surveillance and diagnosis of HCC. Screening should be based in US every 6 months and non-invasive diagnostic criteria of HCC based on imaging findings on dynamic-MR and/or dynamic-CT have been validated and thus, accepted in clinical guidelines. The typical vascular pattern depicted by HCC on CT and or MRI consists on arterial enhancement, stronger than the surrounding liver (wash-in), and hypodensity or hyposignal intensity compared to the surrounding liver (wash-out) in the venous phase. This has a sensitivity of around 60% with a 96-100% specificity. Major improvements on liver imaging have been introduced in the latest years, adding functional information that can be quantified: the use of hepatobiliary contrast media for liver MRI, the inclusion of diffusion-weighted sequences in the standard protocols for liver MRI studies and new radiotracers for positron-emission tomography (PET). However, all them are still a matter of research prior to be incorporated in evidence based clinical decision making. This review summarizes the current knowledge about imaging techniques for the early diagnosis and staging of HCC, and it discusses the most relevant open questions.
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Affiliation(s)
- Carmen Ayuso
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain.
| | - Jordi Rimola
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Ramón Vilana
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Marta Burrel
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Anna Darnell
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Ángeles García-Criado
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Luis Bianchi
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Ernest Belmonte
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Carla Caparroz
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Marta Barrufet
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Jordi Bruix
- Barcelona Clinic Liver Cancer (BCLC) Group: Liver Unit. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
| | - Concepción Brú
- Barcelona Clinic Liver Cancer (BCLC) Group: Radiology Department. Hospital Clínic, University of Barcelona. CIBER ehd. Spain
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Joint analysis of multiple high-dimensional data types using sparse matrix approximations of rank-1 with applications to ovarian and liver cancer. BioData Min 2016; 9:24. [PMID: 27478503 PMCID: PMC4966782 DOI: 10.1186/s13040-016-0103-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2016] [Accepted: 07/05/2016] [Indexed: 12/15/2022] Open
Abstract
Background Technological advances enable the cost-effective acquisition of Multi-Modal Data Sets (MMDS) composed of measurements for multiple, high-dimensional data types obtained from a common set of bio-samples. The joint analysis of the data matrices associated with the different data types of a MMDS should provide a more focused view of the biology underlying complex diseases such as cancer that would not be apparent from the analysis of a single data type alone. As multi-modal data rapidly accumulate in research laboratories and public databases such as The Cancer Genome Atlas (TCGA), the translation of such data into clinically actionable knowledge has been slowed by the lack of computational tools capable of analyzing MMDSs. Here, we describe the Joint Analysis of Many Matrices by ITeration (JAMMIT) algorithm that jointly analyzes the data matrices of a MMDS using sparse matrix approximations of rank-1. Methods The JAMMIT algorithm jointly approximates an arbitrary number of data matrices by rank-1 outer-products composed of “sparse” left-singular vectors (eigen-arrays) that are unique to each matrix and a right-singular vector (eigen-signal) that is common to all the matrices. The non-zero coefficients of the eigen-arrays identify small subsets of variables for each data type (i.e., signatures) that in aggregate, or individually, best explain a dominant eigen-signal defined on the columns of the data matrices. The approximation is specified by a single “sparsity” parameter that is selected based on false discovery rate estimated by permutation testing. Multiple signals of interest in a given MDDS are sequentially detected and modeled by iterating JAMMIT on “residual” data matrices that result from a given sparse approximation. Results We show that JAMMIT outperforms other joint analysis algorithms in the detection of multiple signatures embedded in simulated MDDS. On real multimodal data for ovarian and liver cancer we show that JAMMIT identified multi-modal signatures that were clinically informative and enriched for cancer-related biology. Conclusions Sparse matrix approximations of rank-1 provide a simple yet effective means of jointly reducing multiple, big data types to a small subset of variables that characterize important clinical and/or biological attributes of the bio-samples from which the data were acquired. Electronic supplementary material The online version of this article (doi:10.1186/s13040-016-0103-7) contains supplementary material, which is available to authorized users.
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Hoogenboom TC, Thursz M, Aboagye EO, Sharma R. Functional imaging of hepatocellular carcinoma. Hepat Oncol 2016; 3:137-153. [PMID: 30191034 DOI: 10.2217/hep-2015-0005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2015] [Accepted: 01/20/2016] [Indexed: 02/06/2023] Open
Abstract
Imaging plays a key role in the clinical management of hepatocellular carcinoma (HCC), but conventional imaging techniques have limited sensitivity in visualizing small tumors and assessing response to locoregional treatments and sorafenib. Functional imaging techniques allow visualization of organ and tumor physiology. Assessment of functional characteristics of tissue, such as metabolism, proliferation and stiffness, may overcome some of the limitations of structural imaging. In particular, novel molecular imaging agents offer a potential tool for early diagnosis of HCC, and radiomics may aid in response assessment and generate prognostic models. Further prospective research is warranted to evaluate emerging techniques and their cost-effectiveness in the context of HCC in order to improve detection and response assessment.
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Affiliation(s)
- Tim Ch Hoogenboom
- Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK.,Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK
| | - Mark Thursz
- Department of Hepatology, Imperial College NHS Trust, 10th Floor, Norfolk Place, St Mary's Hospital, London, UK.,Department of Hepatology, Imperial College NHS Trust, 10th Floor, Norfolk Place, St Mary's Hospital, London, UK
| | - Eric O Aboagye
- Comprehensive Cancer Imaging Centre at Imperial College, Faculty of Medicine, Imperial College London, GN1, Ground Floor, Commonwealth building, Hammersmith Campus, London, UK.,Comprehensive Cancer Imaging Centre at Imperial College, Faculty of Medicine, Imperial College London, GN1, Ground Floor, Commonwealth building, Hammersmith Campus, London, UK
| | - Rohini Sharma
- Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK.,Department of Experimental Medicine, Imperial College London, Hammersmith Hospital, Du Cane Road, London, W12 0HS, UK
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Wang X, Tu M, Yan K, Li P, Pang L, Gong Y, Li Q, Liu R, Xu Z, Xu H, Chu PK. Trifunctional Polymeric Nanocomposites Incorporated with Fe₃O₄/Iodine-Containing Rare Earth Complex for Computed X-ray Tomography, Magnetic Resonance, and Optical Imaging. ACS APPLIED MATERIALS & INTERFACES 2015; 7:24523-24532. [PMID: 26484385 DOI: 10.1021/acsami.5b08802] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/05/2023]
Abstract
In this study, a novel polymerizable CT contrast agent integrating iodine with europium(III) has been developed by a facile and universal coordination chemistry method. The Fe3O4 nanoparticles are then incorporated into this iodine-containing europium complex by seed-emulsifier-free polymerization. The nanocomposites combining the difunctional complex and superparamagnetic Fe3O4 nanoparticles, which have uniform size dispersion and high encapsulation rate, are suitable for computed X-ray tomography (CT), magnetic resonance imaging (MRI), and optical imaging. They possess good paramagnetic properties with a maximum saturation magnetization of 2.16 emu/g and a transverse relaxivity rate of 260 mM(-1) s(-1), and they exhibit obvious contrast effects with an iodine payload less than 4.8 mg I/mL. In the in vivo optical imaging assessment, vivid fluorescent dots can be observed in the liver and spleen by two-photon confocal scanning laser microscopy (CLSM). All the results showed that nanocomposites as polymeric trifunctional contrast agents have great clinical potential in CT, MR, and optical imaging.
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Affiliation(s)
- Xin Wang
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for The Green Preparation and Application of Functional Materials, Hubei University , Wuhan, Hubei 430062, China
| | - Mengqi Tu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei 430030, China
| | - Kai Yan
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for The Green Preparation and Application of Functional Materials, Hubei University , Wuhan, Hubei 430062, China
| | - Penghui Li
- Department of Physics and Materials Science, City University of Hong Kong , Tat Chee Avenue, Kowloon, Hong Kong, China
| | - Long Pang
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for The Green Preparation and Application of Functional Materials, Hubei University , Wuhan, Hubei 430062, China
| | - Ying Gong
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for The Green Preparation and Application of Functional Materials, Hubei University , Wuhan, Hubei 430062, China
| | - Qing Li
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for The Green Preparation and Application of Functional Materials, Hubei University , Wuhan, Hubei 430062, China
| | - Ruiqing Liu
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for The Green Preparation and Application of Functional Materials, Hubei University , Wuhan, Hubei 430062, China
| | - Zushun Xu
- Hubei Collaborative Innovation Center for Advanced Organic Chemical Materials, Ministry of Education Key Laboratory for The Green Preparation and Application of Functional Materials, Hubei University , Wuhan, Hubei 430062, China
| | - Haibo Xu
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology , Wuhan, Hubei 430030, China
| | - Paul K Chu
- Department of Physics and Materials Science, City University of Hong Kong , Tat Chee Avenue, Kowloon, Hong Kong, China
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Hartenbach M, Weber S, Albert NL, Hartenbach S, Hirtl A, Zacherl MJ, Paprottka PM, Tiling R, Bartenstein P, Hacker M, Haug AR. Evaluating Treatment Response of Radioembolization in Intermediate-Stage Hepatocellular Carcinoma Patients Using 18F-Fluoroethylcholine PET/CT. J Nucl Med 2015; 56:1661-6. [PMID: 26405170 DOI: 10.2967/jnumed.115.158758] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2015] [Accepted: 08/17/2015] [Indexed: 12/15/2022] Open
Abstract
UNLABELLED The aim of this study was to evaluate (18)F-fluoroethylcholine PET/CT as a metabolic imaging technique for the assessment of treatment response to (90)Y radioembolization in patients with locally advanced hepatocellular carcinoma (HCC). METHODS Thirty-four HCC patients undergoing 78 (18)F-fluoroethylcholine PET/CT scans were identified for this study. Patients with initial or follow-up metastastic disease (n = 9) were excluded at the time point of the metastatic occurrence as well as patients with negative α-fetoprotein (AFP; n = 1), resulting in 24 patients and 57 scans that were eligible. All patients were scheduled for radioembolization and underwent 1 pretherapeutic and at least 1 posttherapeutic (18)F-fluoroethylcholine PET/CT scan. Volume-of-interest analysis and volume-of-interest subtractions were performed. Maximum, mean, and peak standardized uptake value (SUV) analysis was performed, and the total intrahepatic (18)F-fluoroethylcholine positive tumor volume (FEC-PTV) and tumor-to-background ratio were assessed. Statistical analysis was performed using a decreasing AFP of at least 20% as a standard of reference for therapy response including receiver-operating-characteristic analyses as well as descriptive and correlation analyses and multiple logistic regression. RESULTS Fourteen follow-up examinations were categorized as responder and 19 follow-up examinations as nonresponder. Absolute AFP values did not correlate with SUV parameters (P = 0.055). In receiver-operating-characteristic analyses, the initial mean SUV, Δmaximum SUV, and Δtumor-to-background ratio demonstrated the highest area under the curve, 0.84 (P = 0.009), 0.83 (P = 0.011), and 0.83 (P = 0.012), respectively, resulting in a positive prediction of 82%, 83%, and 91% at the respective cutoff points. When multiple logistic regression analysis was applied, this resulted in an area under the curve of 0.90 (P = 0.001), with a positive prediction of 94% and a sensitivity of 94%. The FEC-PTV did not reach significance in the presented dataset. CONCLUSION (18)F-fluoroethylcholine PET/CT demonstrates a high potential for follow-up assessment in the context of radioembolization in patients with locally advanced, but nonmetastatic, HCC and initially elevated AFP, possibly enabling early therapy monitoring independent of morphology.
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Affiliation(s)
- Markus Hartenbach
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Stefan Weber
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Nathalie L Albert
- Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Sabrina Hartenbach
- Institute of Pathology, German Armed Forces Hospital Ulm, Ulm, Germany; and
| | - Albert Hirtl
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Mathias J Zacherl
- Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Philipp M Paprottka
- Department of Clinical Radiology, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Reinhold Tiling
- Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Peter Bartenstein
- Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
| | - Marcus Hacker
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria
| | - Alexander R Haug
- Division of Nuclear Medicine, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, Vienna, Austria Department of Nuclear Medicine, Ludwig-Maximilians-University of Munich, Munich, Germany
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XU ZONGQUAN, YU CHEN, WANG SHUFANG, XU GUOHUI. Transcatheter arterial chemoembolization as an examination method for hepatocellular carcinoma undetected by B-mode ultrasound, computed tomography and digital subtratcion angiography: A case report. Oncol Lett 2015; 10:1759-1762. [PMID: 26622746 PMCID: PMC4533667 DOI: 10.3892/ol.2015.3446] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2014] [Accepted: 04/14/2015] [Indexed: 01/04/2023] Open
Abstract
Transcatheter arterial chemoembolization (TACE) is the conventional treatment for patients with unresectable hepatocellular carcinoma (HCC), but few studies to date have demonstrated the use of TACE as an examination method for uneasily detected HCC. The present study describes an unusual case of HCC with TACE as an examination method. A 41-year-old male presented with an elevated α-fetoprotein level (AFP) of 3,635 ng/ml, however, no tumor lesions were detected by B-mode ultrasound, computed tomography (CT) or digital subtraction angiography. During TACE treatment, two tumor lesions of ~0.5 and 0.8 cm were revealed in the right liver lobe, with no tumors in the left liver lobe. A month after TACE, a liver CT scan found 11 lesions (8 in the right liver lobe and 3 in the left liver lobe). The HCC patient's AFP levels decreased to an almost normal level following the TACE treatment. This study provokes consideration of the application of TACE in the diagnosis and treatment of HCC patients with liver lesions that are hard to detect by conventional means.
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Affiliation(s)
- ZONGQUAN XU
- Department of Hepatic Oncology, Jiangxi Province Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
| | - CHEN YU
- Department of Bone Oncology, Jiangxi Province Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
| | - SHUFANG WANG
- Department of Hepatic Oncology, Jiangxi Province Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
| | - GUOHUI XU
- Department of Hepatic Oncology, Jiangxi Province Cancer Hospital, Nanchang, Jiangxi 330029, P.R. China
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Ruiz I, Féray C. [Current management of hepatocellular carcinoma]. Cancer Radiother 2015; 19:410-5. [PMID: 26337474 DOI: 10.1016/j.canrad.2015.05.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2015] [Accepted: 05/19/2015] [Indexed: 02/06/2023]
Abstract
Hepatocellular carcinoma is the major complication of chronic liver diseases and particularly of cirrhosis whatever its etiology. Once encountered mainly in the endemic countries of hepatitis B and C, the incidence of hepatocellular carcinoma (6/100,000) is parallel to the global development of diabetes, overweight and alcohol consumption. Little progress has been made for this cancer, whose mortality is 100 % at 10 years. Liver transplantation is the only truly curative treatment (survival more than 50 % at 10 years) since it allows the eradication of hepatocellular carcinoma and its essential cause, cirrhotic liver. This is the only possible therapy when liver function is impaired. It has little impact since in the richest countries, less than 10 % of cases can be transplanted. Surgical resection and percutaneous destruction methods (uni- and multipolar radiofrequency, microwave, cryotherapy, electroporation) are the preferred treatments (survival less than 50 % at 5 years) but are only applicable for moderate tumour masses and in the absence of adjuvant therapy, are effective only in the medium term. Most patients received chemoembolization through hepatic artery, whose action is modest. Radiotherapy is widely used in Asia but almost non-existent in Western countries in this indication. Sorafenib is the only effective drug but its impact is modest. Therapies combining two modalities (embolization and radiotherapy; embolization and radiofrequency) seem promising and deserve wider testing. Screening and monitoring of cirrhosis is probably the major measure for potentially curative therapies.
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Affiliation(s)
- I Ruiz
- Service d'hépatologie, hôpital Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France; Équipe 18, Inserm U955, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France
| | - C Féray
- Service d'hépatologie, hôpital Henri-Mondor, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France; Équipe 18, Inserm U955, 51, avenue du Maréchal-de-Lattre-de-Tassigny, 94010 Créteil, France.
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Diagnostic accuracy of 11C-choline PET/CT in comparison with CT and/or MRI in patients with hepatocellular carcinoma. Eur J Nucl Med Mol Imaging 2015; 42:1399-407. [DOI: 10.1007/s00259-015-3079-5] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 04/28/2015] [Indexed: 12/11/2022]
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Cieslak KP, Runge JH, Heger M, Stoker J, Bennink RJ, van Gulik TM. New perspectives in the assessment of future remnant liver. Dig Surg 2014; 31:255-68. [PMID: 25322678 DOI: 10.1159/000364836] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/30/2013] [Accepted: 05/24/2014] [Indexed: 12/20/2022]
Abstract
In order to achieve microscopic radical resection margins and thus better survival, surgical treatment of hepatic tumors has become more aggressive in the last decades, resulting in an increased rate of complex and extended liver resections. Postoperative outcomes mainly depend on the size and quality of the future remnant liver (FRL). Liver resection, when performed in the absence of sufficient FRL, inevitably leads to postresection liver failure. The current gold standard in the preoperative assessment of the FRL is computed tomography volumetry. In addition to the volume of the liver remnant after resection, postoperative function of the liver remnant is directly related to the quality of liver parenchyma. The latter is mainly influenced by underlying diseases such as cirrhosis and steatosis, which are often inaccurately defined until microscopic examination after the resection. Postresection liver failure remains a point of major concern that calls for accurate methods of preoperative FRL assessment. A wide spectrum of tests has become available in the past years, attesting to the fact that the ideal methodology has yet to be defined. The aim of this review is to discuss the current modalities available and new perspectives in the assessment of FRL in patients scheduled for major liver resection.
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Affiliation(s)
- Kasia P Cieslak
- Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands
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Zheng F, Devoogdt N, Sparkes A, Morias Y, Abels C, Stijlemans B, Lahoutte T, Muyldermans S, De Baetselier P, Schoonooghe S, Beschin A, Raes G. Monitoring liver macrophages using nanobodies targeting Vsig4: concanavalin A induced acute hepatitis as paradigm. Immunobiology 2014; 220:200-9. [PMID: 25440182 DOI: 10.1016/j.imbio.2014.09.018] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2014] [Revised: 09/09/2014] [Accepted: 09/23/2014] [Indexed: 12/31/2022]
Abstract
Kupffer cells (KCs) are liver resident macrophages which are important for tissue homeostasis and have been implicated in immunogenic, tolerogenic and pathogenic immune reactions depending on the insult. These cells and the biomarkers they express thus represent interesting in vivo sensors for monitoring liver inflammation. In the current study, we explored whether KCs can be monitored non-invasively using single-photon-emission computed tomography (SPECT) with (99m)Tc labeled nanobodies (Nbs) targeting selected biomarkers. Nbs targeting V-set and immunoglobulin domain-containing 4 (Vsig4) or macrophage mannose receptor (MMR) accumulated in the liver of untreated mice. The liver targeting of anti-Vsig4 Nbs, but not anti-MMR Nbs, was blunted upon depletion of macrophages, highlighting specificity of anti-Vsig4 Nbs for liver macrophage imaging. Ex vivo flow cytometry and immunohistochemistry analysis confirmed that anti-Vsig4 Nbs specifically targeted KCs but no other cell types in the liver. Upon induction of acute hepatitis using concanavalin A (ConA), down-regulation of the in vivo imaging signal obtained using anti-Vsig4 Nbs reflected reduction in KC numbers and transient modulation of Vsig4 expression on KCs. Overall, these results indicate that Nbs targeting Vsig4 as molecular imaging biomarker enable non-invasive monitoring of KCs during hepatic inflammation.
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Affiliation(s)
- Fang Zheng
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium; Department of Biochemistry and Molecular Biology, Health Science Center, Xi'an Jiaotong University, Xi'an, China
| | - Nick Devoogdt
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; In Vivo Cellular and Molecular Imaging Center, Vrije Universiteit Brussel, Brussels, Belgium
| | - Amanda Sparkes
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium
| | - Yannick Morias
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium
| | - Chloé Abels
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium
| | - Benoit Stijlemans
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium
| | - Tony Lahoutte
- In Vivo Cellular and Molecular Imaging Center, Vrije Universiteit Brussel, Brussels, Belgium; Department of Nuclear Medicine, UZ Brussel, Vrije Universtiteit Brussel, Brussels, Belgium
| | - Serge Muyldermans
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Structural Biology Research Center, Vrije Universiteit Brussel, Brussels, Belgium
| | - Patrick De Baetselier
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium
| | - Steve Schoonooghe
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium
| | - Alain Beschin
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium
| | - Geert Raes
- Laboratory of Cellular and Molecular Immunology, Vrije Universiteit Brussel, Brussels, Belgium; VIB Laboratory of Myeloid Cell Immunology, Brussels, Belgium.
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Teixera SR, Kohan AA, Paspulati RM, Rong R, Herrmann KA. Potential Role of Positron Emission Tomography/Magnetic Resonance Imaging in Gastrointestinal and Abdominal Malignancies: Preliminary Experience. Semin Roentgenol 2014; 49:321-33. [DOI: 10.1053/j.ro.2014.07.003] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Bertagna F, Bertoli M, Bosio G, Biasiotto G, Sadeghi R, Giubbini R, Treglia G. Diagnostic role of radiolabelled choline PET or PET/CT in hepatocellular carcinoma: a systematic review and meta-analysis. Hepatol Int 2014. [PMID: 26202754 DOI: 10.1007/s12072-014-9566-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The role of fluorine-18-fluorodeoxygluose positron emission tomography/computed tomography ((18)F-FDG PET/CT) in hepatocellular carcinoma (HCC) has not been firmly established yet and its sensitivity has been reported to be in the range of 40-60 %. Because of this relatively low sensitivity alternative tracers have been proposed. The aim of our review is to analyse the literature data on the diagnostic role of (18)F/(11)C-choline PET/CT in the evaluation of HCC. A comprehensive computer literature search of PubMed/MEDLINE, Embase and Scopus databases was conducted to find relevant published articles about the role of whole-body (18)F-choline or (11)C-choline PET or PET/CT in patients with HCC. Furthermore, a meta-analysis about the detection rate of this method in HCC was performed. Six articles were included in this systematic review and discussed. The meta-analysis of five out of six articles showed a DR of 84 % (95 % CI 79-89 %). The DR increased when poorly differentiated HCC was excluded from the analysis. Radiolabelled choline PET or PET/CT could be a valuable tool in detecting HCC and it is better than (18)F-FDG PET/CT, especially in well to moderately differentiated lesions; on the other hand, poorly differentiated and higher-stage HCC could be better evaluated with (18)F-FDG and dual tracer imaging should be considered and could be potentially useful to increase accuracy.
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Affiliation(s)
- Francesco Bertagna
- Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy.
| | - Mattia Bertoli
- Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy
| | - Giovanni Bosio
- Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy
| | - Giorgio Biasiotto
- Biomedical Technology Department, University of Brescia, Brescia, Italy
| | - Ramin Sadeghi
- Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Raffaele Giubbini
- Nuclear Medicine, University of Brescia and Spedali Civili di Brescia, P.le Spedali Civili, 1, 25123, Brescia, Italy
| | - Giorgio Treglia
- Department of Nuclear Medicine and PET/CT Center, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland
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