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He Y, Rogasch JMM, Savic LJ. PET Imaging and Key Radiotracers for Evaluating Response to Locoregional Therapy in Hepatocellular Carcinoma. PET Clin 2025:S1556-8598(25)00024-0. [PMID: 40287367 DOI: 10.1016/j.cpet.2025.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2025]
Abstract
Locoregional therapies (LRTs) play a considerable role in the management of hepatocellular carcinoma (HCC), especially for patients who are not suitable for radical resection or transplantation. In clinical practice, assessment of LRTs is mainly based on computed tomography and MR imaging, but functional and metabolic information is less accessible. This article reviews the use of various the standardized uptake value parameters based on PET and multiple radiotracers for managing HCC after treatment with different LRTs, as well as parts of preclinical research. It discusses the current use of PET in more detail, as well as its advantages, disadvantages, and prospects.
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Affiliation(s)
- Yubei He
- Department of Radiology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin 13353, Germany; Experimental and Clinical Research Center, A Joint Cooperation of Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Berlin 13125, Germany
| | - Julian M M Rogasch
- Department of Nuclear Medicine, Charité - Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Berlin 10117, Germany
| | - Lynn Jeanette Savic
- Department of Radiology, Campus Virchow-Klinikum, Charité - Universitätsmedizin Berlin, Berlin 13353, Germany; Experimental and Clinical Research Center, A Joint Cooperation of Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Berlin 13125, Germany; Berlin Institute of Health at Charité, Universitätsmedizin Berlin, Berlin 10117, Germany.
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2
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Cai D, He Y, Yu H, Zhang Y, Shi H. Comparative benefits of Ki and SUV images in lesion detection during PET/CT imaging. EJNMMI Res 2024; 14:98. [PMID: 39412599 PMCID: PMC11485003 DOI: 10.1186/s13550-024-01162-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 10/04/2024] [Indexed: 10/19/2024] Open
Abstract
BACKGROUND Clinical application of the tracer net influx rate (Ki) imaging in PET/CT remains limited, due to a lack of evidence demonstrating the superiority of Ki images in lesion detection, and guidelines on when to utilize Ki images. This study aims to compare the benefits of Ki and standardized uptake value (SUV) images in lesion detection during PET/CT imaging. By analyzing the performance of both techniques in identifying tumor lesions, the study seeks to provide guidance for the clinical application of Ki images. RESULTS This retrospective study included 134 patients with 244 pathologically confirmed lesions (200 malignant and 44 benign). Patients with a histopathological diagnosis received a weight-based 18F-FDG injection and underwent 60-min total-body PET/CT dynamic imaging. SUV images were reconstructed using data collected from the last 10 min of the scans. Ki images were generated using the Patlak methods with data from minutes 12-60. The background SUVmax, SUVmean, SUVSD, Kimax, Kimean, and KiSD values were recorded. The signal-to-noise ratios of the SUV (SUVSNR) and Ki (KiSNR) images were calculated. The lesion detection rate and sensitivity of the SUV and Ki images were evaluated. The lesion-detection rates were 97.7% (214/219) and 99.5% (218/219) for the SUV and Ki images, respectively (p = .22). Five false-negative lesions on the SUV images were true-positive on the Ki images (3 hepatic malignancies and 2 metastatic lymph nodes). The sensitivity (94.0% vs. 96.0%, p = .22), specificity (41.9% vs. 41.9%, p > .99), accuracy (84.4% vs. 86.1%, p = .61), positive predictive value (87.9% vs. 88.1%, p = .94), negative predictive value (60.0% vs. 69.2%, p = .47), and the area under the curve [0.68 (95% confidence interval, 0.61-0.73) vs. 0.69 (95% confidence interval, 0.62-0.74)] were similar in the SUV and Ki images (all p ≥ .10). CONCLUSION Ki images exhibit benefits in lesion detection compared to SUV images, particularly in organs with high background such as liver. The enhanced contrast provided by Ki imaging is recommended to clinically improve detection rates in such cases.
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Affiliation(s)
- Danjie Cai
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Nuclear Medicine Institute of Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Yibo He
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Nuclear Medicine Institute of Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Haojun Yu
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Nuclear Medicine Institute of Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Yiqiu Zhang
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China
- Nuclear Medicine Institute of Fudan University, Shanghai, 200032, China
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China
| | - Hongcheng Shi
- Department of Nuclear Medicine, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
- Nuclear Medicine Institute of Fudan University, Shanghai, 200032, China.
- Shanghai Institute of Medical Imaging, Shanghai, 200032, China.
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He J, Wang T, Li Y, Deng Y, Wang S. Dynamic chaotic gravitational search algorithm-based kinetic parameter estimation of hepatocellular carcinoma on 18F-FDG PET/CT. BMC Med Imaging 2022; 22:20. [PMID: 35125095 PMCID: PMC8818192 DOI: 10.1186/s12880-022-00742-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Accepted: 01/24/2022] [Indexed: 11/16/2022] Open
Abstract
Background Kinetic parameters estimated with dynamic 18F-FDG PET/CT can help to characterize hepatocellular carcinoma (HCC). We aim to evaluate the feasibility of the gravitational search algorithm (GSA) for kinetic parameter estimation and to propose a dynamic chaotic gravitational search algorithm (DCGSA) to enhance parameter estimation. Methods Five-minute dynamic PET/CT data of 20 HCCs were prospectively enrolled, and the kinetic parameters k1 ~ k4 and the hepatic arterial perfusion index (HPI) were estimated with a dual-input three-compartment model based on nonlinear least squares (NLLS), GSA and DCGSA. Results The results showed that there were significant differences between the HCCs and background liver tissues for k1, k4 and the HPI of NLLS; k1, k3, k4 and the HPI of GSA; and k1, k2, k3, k4 and the HPI of DCGSA. DCGSA had a higher diagnostic performance for k3 than NLLS and GSA. Conclusions GSA enables accurate estimation of the kinetic parameters of dynamic PET/CT in the diagnosis of HCC, and DCGSA can enhance the diagnostic performance.
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Affiliation(s)
- Jianfeng He
- Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Yunnan Key Laboratory of Artificial Intelligence, Kunming, 650500, Yunnan, China
| | - Tao Wang
- Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Yunnan Key Laboratory of Artificial Intelligence, Kunming, 650500, Yunnan, China
| | - Yongjin Li
- Faculty of Information Engineering and Automation, Kunming University of Science and Technology, Yunnan Key Laboratory of Artificial Intelligence, Kunming, 650500, Yunnan, China
| | - Yinglei Deng
- PET/CT Center, Affiliated Hospital of Kunming University of Science and Technology, First People's Hospital of Yunnan, Kunming, 650031, China
| | - Shaobo Wang
- PET/CT Center, Affiliated Hospital of Kunming University of Science and Technology, First People's Hospital of Yunnan, Kunming, 650031, China.
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Sureka B, Rastogi A, Mukund A, Sarin SK. False-positive 18F fluorodeoxyglucose positron emission tomography-avid benign hepatic tumor: Previously unreported in a male patient. Indian J Radiol Imaging 2021; 28:200-204. [PMID: 30050244 PMCID: PMC6038214 DOI: 10.4103/ijri.ijri_170_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
We report a case of 18F fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography-avid histologically confirmed inflammatory hepatic adenoma in a 77-year-old male patient without any history of steroid, alcohol use. This is the first case report of inflammatory hepatic adenoma in a male patient documented in the published literature showing uptake on 18F-FDG PET. Previous single case report of 18F-FDG PET-avid hepatic adenoma in a male patient was of hepatocyte nuclear factor-1-α subtype.
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Affiliation(s)
- Binit Sureka
- Department of Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Archana Rastogi
- Department of Pathology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Amar Mukund
- Department of Radiology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Shiv Kumar Sarin
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
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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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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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Small Bowel Metastasis From Hepatocellular Carcinoma Detected by 18F-FDG PET/CT But Not by 11C-Acetate PET/CT. Clin Nucl Med 2017; 42:966-967. [PMID: 29076914 DOI: 10.1097/rlu.0000000000001882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Gastrointestinal tract is rarely a metastatic site of hepatocellular carcinoma (HCC). We present a 43-year-old woman with small bowel metastasis from HCC in which metastasis was detected using F-FDG PET/CT. However, the site of metastasis showed no significant uptake on C-acetate PET/CT. C-acetate PET/CT has a limited value in HCC patients with suspected extrahepatic metastasis, compared with F-FDG PET/CT.
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Kornberg A, Schernhammer M, Friess H. 18F-FDG-PET for Assessing Biological Viability and Prognosis in Liver Transplant Patients with Hepatocellular Carcinoma. J Clin Transl Hepatol 2017; 5:224-234. [PMID: 28936404 PMCID: PMC5606969 DOI: 10.14218/jcth.2017.00014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2017] [Revised: 05/18/2017] [Accepted: 06/05/2017] [Indexed: 12/12/2022] Open
Abstract
Liver transplantation (LT) has become standard of care in patients with non-resectable early stage hepatocellular carcinoma (HCC) in liver cirrhosis. Currently, patient selection for LT is strictly based on tumor size and number, provided by the Milan criteria. This may, however, exclude patients with advanced tumor load but favourable biology from a possibly curative treatment option. It became clear in recent years that biological tumor viability rather than tumor macromorphology determines posttransplant outcome. In particular, microvascular invasion and poor grading reflect tumor aggressiveness and promote the risk of tumor relapse. Pretransplant biopsy is not applicable due to tumor heterogeneity and risk of tumor cell seeding. 18F-fludeoxyglucose (18F-FDG) positron emission tomography (PET), an established nuclear imaging device in oncology, was demonstrated to non-invasively correlate with unfavorable histopathologic features. Currently, there is an increasing amount of evidence that 18F-FDG-PET is very useful for identifying eligible liver transplant patients with HCC beyond standard criteria but less aggressive tumor properties. In order to safely expand the HCC selection criteria and the pool of eligible liver recipients, tumor evaluation with 18F-FDG-PET should be implemented in pretransplant decision process.
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Affiliation(s)
- Arno Kornberg
- *Correspondence to: Arno Kornberg, Department of Surgery, Klinikum rechts der Isar, Technical University Munich, Ismaningerstr. 22, D-81675 Munich, Germany. Tel: +89-41405087, Fax: +89-41404884, E-mail:
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10
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Baxa J, Ferdova E, Ferda J. PET/MRI of the thorax, abdomen and retroperitoneum: Benefits of the breathing-synchronized scanning. Eur J Radiol 2017; 94:A35-A43. [PMID: 28274619 DOI: 10.1016/j.ejrad.2017.02.038] [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: 01/04/2017] [Accepted: 02/23/2017] [Indexed: 01/16/2023]
Abstract
Hybrid imaging using various radiopharmaceuticals is currently essential not only in detection and therapy response monitoring of tumors, but also in assessment of inflammatory or systemic diseases. Combination of positron emission tomography (PET) and magnetic resonance imaging (MRI) is still relatively new method with great prospects of comprehensive assessment using anatomical and multiple functional information. However, benefits of PET/MRI in thorax, abdomen and retroperitoneum are not completely defined. Breathing movements affect imaging of thoracic, abdominal and retroperitoneal organs and pathological structures using PET and MRI. Fast MRI sequences are performed using breath-hold technique; however, acquisition of longer sequences and PET scanning need to be breathing-synchronized. Review article summarizes concrete PET/MRI protocols and importance of concrete MRI sequences and radiopharmaceuticals in different pathological lesions with focus on benefit of breathing-synchronized techniques.
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Affiliation(s)
- Jan Baxa
- Department of Imaging Methods, University Hospital Pilsen,Czech Republic; Faculty of Medicine in Pilsen, Charles University, Czech Republic.
| | - Eva Ferdova
- Department of Imaging Methods, University Hospital Pilsen,Czech Republic
| | - Jiří Ferda
- Department of Imaging Methods, University Hospital Pilsen,Czech Republic; Faculty of Medicine in Pilsen, Charles University, Czech Republic
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Ye XD, Yuan Z, Zhang J, Yuan Z. Radiological biomarkers for assessing response to locoregional therapies in hepatocellular carcinoma: From morphological to functional imaging (Review). Oncol Rep 2017; 37:1337-1346. [PMID: 28184942 DOI: 10.3892/or.2017.5420] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2016] [Accepted: 01/16/2017] [Indexed: 11/05/2022] Open
Abstract
Many hepatocellular carcinoma (HCC) patients do not qualify for curative surgical intervention and are instead treated with locoregional therapies (LRTs) including ablative and endovascular therapies. Assessment of imaging response is essential in the management of HCC for determining efficacy of therapy and as a surrogate marker for improved survival. The established morphological image biomarkers for tumor burden measurement continue to be applied, as size measurement can easily be used in clinical practice. However, in the setting of liver-directed LRTs for HCC, simple tumor morphological changes can be less informative and usually appear later than biologic changes. Functional imaging (such as perfusion and diffusion imaging, PET-CT/MR and MR spectroscopy) has the potential to be a promising technique for assessment of HCC response to LRTs. Although promising, none of these functional imaging biomarkers have gone through all the required steps of standardization and validation and established accepted criteria for clinical practice.
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Affiliation(s)
- Xiao-Dan Ye
- Department of Radiology, Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, Shanghai 200030, P.R. China
| | - Zuguo Yuan
- Radiation Oncology Center, The 1st Affiliated Hospital of Zhejiang University, Hangzhou, Zhejiang 310000, P.R. China
| | - Jian Zhang
- Department of Nuclear Medicine, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China
| | - Zheng Yuan
- Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai 200032, P.R. China
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Fat-Containing Hypermetabolic Masses on FDG PET/CT: A Spectrum of Benign and Malignant Conditions. AJR Am J Roentgenol 2016; 207:1095-1104. [PMID: 27490138 DOI: 10.2214/ajr.16.16066] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVE This article focuses on identifying the imaging appearances of hypermetabolic fatty masses and masslike lesions on PET/CT and understanding the diagnostic challenges radiologists may face while interpreting findings of these lesions on PET/CT. This article provides an approach to aid in the diagnosis of these lesions and the appropriate management of patients. CONCLUSION Both malignant and benign fat-containing masses and masslike lesions can show hypermetabolic activity on PET/CT. Although the differential diagnosis is broad, clinical history, anatomic location, and knowledge of anatomic variants and imaging features can help radiologists avoid misinterpretation of benign fatty lesions as malignancy.
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Wachsmann J, Peng F. Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma. World J Gastroenterol 2016; 22:221-231. [PMID: 26755872 PMCID: PMC4698487 DOI: 10.3748/wjg.v22.i1.221] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2015] [Revised: 10/18/2015] [Accepted: 11/13/2015] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide. Significant efforts have been devoted to identify new biomarkers for molecular imaging and targeted therapy of HCC. Copper is a nutritional metal required for the function of numerous enzymatic molecules in the metabolic pathways of human cells. Emerging evidence suggests that copper plays a role in cell proliferation and angiogenesis. Increased accumulation of copper ions was detected in tissue samples of HCC and many other cancers in humans. Altered copper metabolism is a new biomarker for molecular cancer imaging with position emission tomography (PET) using radioactive copper as a tracer. It has been reported that extrahepatic mouse hepatoma or HCC xenografts can be localized with PET using copper-64 chloride as a tracer, suggesting that copper metabolism is a new biomarker for the detection of HCC metastasis in areas of low physiological copper uptake. In addition to copper modulation therapy with copper chelators, short-interference RNA specific for human copper transporter 1 (hCtr1) may be used to suppress growth of HCC by blocking increased copper uptake mediated by hCtr1. Furthermore, altered copper metabolism is a promising target for radionuclide therapy of HCC using therapeutic copper radionuclides. Copper metabolism has potential as a new theranostic biomarker for molecular imaging as well as targeted therapy of HCC.
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Lee SY, Kingham TP, LaGratta MD, Jessurun J, Cherqui D, Jarnagin WR, Kluger MD. PET-avid hepatocellular adenomas: incidental findings associated with HNF1-α mutated lesions. HPB (Oxford) 2016; 18:41-8. [PMID: 26776850 PMCID: PMC4750225 DOI: 10.1016/j.hpb.2015.07.001] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Revised: 07/06/2015] [Accepted: 07/07/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Hepatocellular adenoma (HCA) is the second most common benign liver neoplasm and occurs predominantly in women in their reproductive years. Positron emission tomography (PET) using [18F] fluorodeoxyglucose (FDG) is commonly used in cancer staging, surveillance and evaluation of treatment response. PET-avid HCA are rare and can be falsely interpreted as malignancies. METHODS A retrospective review of four institutions' database was performed to identify the PET-avid HCAs with clinico-pathological correlation. RESULTS Nine patients with histological proven PET-avid HCA was identified. Eight out of 9 patients were female with a median age at diagnosis of 44 years. All patients' tumors with available histological subtyping (8/8) were HNF1-α mutated and had no inflammatory changes; 6 out the 9 lesions had prominent (>50%) steatotic changes. CONCLUSION Hepatocellular adenomas, specifically the HNF1-α subtype, can cause false-positive PET findings when seeking to identify malignancy. Concomitantly, PET-CT may have the potential to identify the HCA histopathologic variant with the lowest malignant and hemorrhagic potential.
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Affiliation(s)
- Ser Yee Lee
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States,Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore
| | - T. Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Maria D. LaGratta
- New York-Presbyterian Hospital – Weill Cornell Medical Center, Diagnostic Radiology, 1305 York Avenue, New York, NY 10021, United States
| | - Jose Jessurun
- New York Presbyterian Hospital – Weill Cornell Medical College, Surgical Pathology, 525 East 68th Street, New York, NY 10065, United States
| | - Daniel Cherqui
- Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - William R. Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, United States
| | - Michael D. Kluger
- New York Presbyterian Hospital Columbia Presbyterian Medical Center, Department of Surgery, 161 Fort Washington Avenue 823, New York, NY 10024, United States,Correspondence Michael D. Kluger, New York Presbyterian Hospital Columbia Presbyterian Medical Center, Department of Surgery, 161 Fort Washington Avenue 823, New York, NY 10024, United States.
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15
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Lee SY, Kingham TP, LaGratta MD, Jessurun J, Cherqui D, Jarnagin WR, Kluger MD. PET-avid hepatocellular adenomas: incidental findings associated with HNF1-α mutated lesions. HPB (Oxford) 2015:n/a-n/a. [PMID: 26472264 DOI: 10.1111/hpb.12489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2015] [Accepted: 07/07/2015] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hepatocellular adenoma (HCA) is the second most common benign liver neoplasm and occurs predominantly in women in their reproductive years. Positron-emission tomography (PET) using [18F] fluorodeoxyglucose (FDG) is commonly used in cancer staging, surveillance and evaluation of the treatment response. PET-avid HCA is rare and can be falsely interpreted as malignancies. METHODS A retrospective review of four institutions' database was performed to identify the PET-avid HCAs with clinico-pathological correlation. RESULTS Nine patients with histological proven PET-avid HCA was identified. Eight out of nine patients were female with a median age at diagnosis of 44 years. All patients' tumours with available histological subtyping (8/8) were HNF1-α mutated and had no inflammatory changes; six out the nine lesions had prominent (>50%) steatotic changes. CONCLUSION Hepatocellular adenomas, specifically the HNF1-α subtype, can cause false-positive PET findings when seeking to identify malignancy. Concomitantly, PET-CT may have the potential to identify the HCA histopathological variant with the lowest malignant and haemorrhagic potential.
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Affiliation(s)
- Ser Yee Lee
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, New York Presbyterian Hospital Weill-Cornell Medical Center, New York, NY, USA
- Department of Hepatopancreatobiliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore
| | - T Peter Kingham
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Maria D LaGratta
- Diagnostic Radiology, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, NY, USA
| | - Jose Jessurun
- Surgical Pathology, New York Presbyterian Hospital - Weill Cornell Medical College, New York, NY, USA
| | - Daniel Cherqui
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, New York Presbyterian Hospital Weill-Cornell Medical Center, New York, NY, USA
- Hôpital Paul Brousse, Centre Hépato-Biliaire, Villejuif, France
| | - William R Jarnagin
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Michael D Kluger
- Department of Surgery, Section of Hepatobiliary Surgery and Liver Transplantation, New York Presbyterian Hospital Weill-Cornell Medical Center, New York, NY, USA
- Department of Surgery, New York Presbyterian Hospital Columbia Presbyterian Medical Center, New York, NY, USA
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Wang SB, Wu HB, Wang QS, Zhou WL, Tian Y, Li HS, Ji YH, Lv L. Combined early dynamic (18)F-FDG PET/CT and conventional whole-body (18)F-FDG PET/CT provide one-stop imaging for detecting hepatocellular carcinoma. Clin Res Hepatol Gastroenterol 2015; 39:324-30. [PMID: 25487755 DOI: 10.1016/j.clinre.2014.10.010] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2014] [Revised: 10/12/2014] [Accepted: 10/21/2014] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE It is widely accepted that conventional (18)F-FDG PET/CT (whole-body static (18)F-FDG PET/CT, WB (18)F-FDG PET/CT) has a low detection rate for hepatocellular carcinoma (HCC). We prospectively assessed the role of early dynamic (18)F-FDG PET/CT (ED (18)F-FDG PET/CT) and WB (18)F-FDG PET/CT in detecting HCC, and we quantified the added value of ED (18)F-FDG PET/CT to WB (18)F-FDG PET/CT. METHODS Twenty-two patients with 37 HCC tumors (HCCs) who underwent both a liver ED (18)F-FDG PET/CT (performed simultaneously with a 5.5 MBq/kg (18)F-FDG bolus injection and continued for 240 s) and a WB (18)F-FDG PET/CT were enrolled in the study. RESULTS The WB (18)F-FDG PET/CT and ED (18)F-FDG PET/CT scans were positive in 56.7% (21/37) and 78.4% (29/37) HCCs, respectively (P<0.05). ED (18)F-FDG PET/CT in conjunction with WB (18)F-FDG PET/CT (one-stop (18)F-FDG PET/CT) improved the positive detection rates of WB and ED (18)F-FDG PET/CT alone from 56.7% and 78.4% to 91.9% (34/37) (P<0.001 and P>0.05, respectively). CONCLUSION One-stop (18)F-FDG PET/CT appears to be useful to improve WB (18)F-FDG PET/CT for HCC detection.
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Affiliation(s)
- Shao-Bo Wang
- NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Radiology, First People's Hospital of Yunnan Province, Kunming, China.
| | - Hu-Bing Wu
- NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Quan-Shi Wang
- NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
| | - Wen-Lan Zhou
- NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Ying Tian
- NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Hong-Sheng Li
- NanFang PET Center, Nanfang Hospital, Southern Medical University, Guangzhou, China
| | - Yun-Hai Ji
- Department of Radiology, First People's Hospital of Yunnan Province, Kunming, China
| | - Liang Lv
- Department of Radiology, First People's Hospital of Yunnan Province, Kunming, China
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Jang HY, Kwon SY, Pyo A, Hur MG, Kim SW, Park JH, Kim HJ, Yang SD, Lee S, Kim DY, Min JJ. In-house development of an optimized synthetic module for routine [11C]acetate production. Nucl Med Commun 2015; 36:102-6. [PMID: 25244351 PMCID: PMC4243701 DOI: 10.1097/mnm.0000000000000213] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2014] [Revised: 08/20/2014] [Accepted: 08/20/2014] [Indexed: 11/26/2022]
Abstract
[11C]Acetate, a radiotracer for PET imaging, is a promising radiopharmaceutical for overcoming the limitation of 2-deoxy-2-[18F]fluoro-D-glucose in a number of cancers. Here, the optimized automatic synthesis of [11C]acetate using an in-house-developed module under different conditions has been reported for routine production. [11C]CO2 was produced in a 16.4 MeV PETtrace cyclotron, and methyl magnesium chloride was used for synthesis. For product purification, ion-exchange solid-phase extraction cartridges were used, connected in series. High-performance liquid chromatography and gas chromatography were used to measure radiochemical and chemical purity. The Limulus amebocyte lysate test and the fluid thioglycollate medium test were performed for quality control of [11C]acetate. The total reaction time of [11C]acetate was within 15 min, and the overall decay-corrected radiochemical yield was 84.33±8.85%. Radiochemical purity was greater than 98% when evaluated on an analytical high-performance liquid chromatography system. No endotoxins or anaerobic bacteria were seen on quality control checks. Optimized production of [11C]acetate was achieved by the in-house module. Radiochemical and biological properties of the [11C]acetate produced were appropriate for clinical PET study.
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Affiliation(s)
- Hwa Youn Jang
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun
- Department of Chemistry, Chonnam National University, Gwangju
| | - Seong Young Kwon
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun
| | - Ayoung Pyo
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun
- Department of Chemistry, Chonnam National University, Gwangju
| | - Min Goo Hur
- Radiation Instrumentation Research Division, Korea Atomic Energy Research Institute, Jeongeup
| | - Sang Wook Kim
- Department of Advanced Materials Chemistry, College of Sciences & Technology, Dongguk University-GyeongJu, GyeongJu, Republic of Korea
| | - Jeong-Hoon Park
- Radiation Instrumentation Research Division, Korea Atomic Energy Research Institute, Jeongeup
| | - Hee-Jung Kim
- Radiation Instrumentation Research Division, Korea Atomic Energy Research Institute, Jeongeup
| | - Seung Dae Yang
- Radiation Instrumentation Research Division, Korea Atomic Energy Research Institute, Jeongeup
| | - Sunwoo Lee
- Department of Chemistry, Chonnam National University, Gwangju
| | - Dong-Yeon Kim
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun
| | - Jung-Joon Min
- Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun
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18
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F-18 Choline PET angiography of the pelvic arteries: evaluation of image quality and comparison with contrast-enhanced CT. Clin Imaging 2014; 39:437-41. [PMID: 25457527 DOI: 10.1016/j.clinimag.2014.08.007] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2014] [Revised: 08/09/2014] [Accepted: 08/15/2014] [Indexed: 02/01/2023]
Abstract
PURPOSE The purpose was to show the feasibility of F-18 choline positron emission tomography (PET) angiography for the evaluation of abdominal and iliac arteries. METHODS Thirty-five patients were examined and image quality was scored. Findings were correlated with contrast-enhanced computed tomography. RESULTS Image quality was best in the aorta and common iliac arteries (100% and 93% of vessels). Negative predictive values of PET angiography were excellent (100%), and positive predictive values were impaired by disease overestimation. CONCLUSION PET angiography is technically feasible and of good image quality in large arteries. In selected cases, it may become an alternative to established angiographic methods.
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Drescher R, Freesmeyer M. F-18 fluorodeoxyglucose PET angiography of the abdominal arteries: evaluation of image quality and comparison with contrast-enhanced CT. Ann Nucl Med 2014; 29:198-205. [DOI: 10.1007/s12149-014-0930-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2014] [Accepted: 11/09/2014] [Indexed: 10/24/2022]
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20
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Kawamura E, Shiomi S, Kotani K, Kawabe J, Hagihara A, Fujii H, Uchida-Kobayashi S, Iwai S, Morikawa H, Enomoto M, Murakami Y, Tamori A, Kawada N. Positioning of 18F-fluorodeoxyglucose-positron emission tomography imaging in the management algorithm of hepatocellular carcinoma. J Gastroenterol Hepatol 2014; 29:1722-1727. [PMID: 24730671 DOI: 10.1111/jgh.12611] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/19/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND AND AIM (18) F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) may detect primary lesions (PLs) and extrahepatic metastases (EHMs) only in advanced hepatocellular carcinoma (HCC) patients. We investigated the requirement of PET and the optimal timing of PET scanning for accurate staging and treatment planning. METHODS We conducted a retrospective investigation of 64 HCC patients who underwent PET (median age, 74 years; male/female, 41/23; etiology, 46 hepatitis C virus/4 hepatitis B virus/4 alcoholic/10 others). To determine the best timing for PET examinations, we analyzed PET result-based recommended treatment changes and characteristics of patients with FDG-avid PLs or EHMs. RESULTS FDG-avid PLs were detected by PET in 22 patients (34%): 18 with hypervascular PL, 11 with serum α-fetoprotein levels ≥ 200 ng/mL, and 11 beyond Milan criteria. EHMs were detected in 21 patients (33%: lymph nodes, 8; lung, 5; abdominal wall, 4; bone, 3; other organs, 4 [including overlapping]). Recommended treatments changed for 16 patients (25%) because of Barcelona Clinic Liver Cancer stage increases based on PET scanning. In multivariate analyses, serum α-fetoprotein levels ≥ 200 ng/mL and beyond Milan criteria were independent factors for FDG-avid PLs and a maximum standardized uptake value (SUVmax) of PLs of ≥ 4.0 was an independent factor for FDG-avid EHMs (P = 0.002, 0.008, and 0.045, respectively). CONCLUSIONS PET allows detection of HCC spread in patients with elevated serum α-fetoprotein levels or those beyond Milan criteria and detects EHMs in patients with PLs with high SUVmax values. Optimally timed PET scans can complement conventional imaging for accurate staging and treatment strategy determination.
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Affiliation(s)
- Etsushi Kawamura
- Department of Hepatology, Graduate School of Medicine, Osaka City University, Osaka, Japan
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Dai T, Popa E, Shah MA. The Role of 18F-FDG PET Imaging in Upper Gastrointestinal Malignancies. Curr Treat Options Oncol 2014; 15:351-64. [DOI: 10.1007/s11864-014-0301-9] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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22
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Wang XY, Chen D, Zhang XS, Chen ZF, Hu AB. Value of ¹⁸F-FDG-PET/CT in the detection of recurrent hepatocellular carcinoma after hepatectomy or radiofrequency ablation: a comparative study with contrast-enhanced ultrasound. J Dig Dis 2013; 14:433-8. [PMID: 23615075 DOI: 10.1111/1751-2980.12064] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate the role of positron emission tomography/computer tomography with fluorine-18 fluorodeoxyglucose ((18) F-FDG-PET/CT) in detecting hepatocellular carcinoma (HCC) recurrence after hepatectomy and/or radiofrequency ablation (RFA) and to compare its efficacy with contrast-enhanced ultrasound (CEUS). METHODS A total of 36 HCC patients were included in this study. All patients underwent both (18) F-FDG-PET/CT and CEUS at least once for the diagnosis of HCC recurrence. The time interval between PET/CT and CEUS was 14 ± 3 days. All patients were followed up for at least 24 months. RESULTS In all, 32 patients were confirmed to have HCC recurrence by pathology and clinical follow-up. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy of (18) F-FDG-PET/CT for intrahepatic HCC recurrence were 96.7%, 83.3%, 96.7%, 83.3% and 94.4%, respectively. The corresponding values of CEUS were 56.7%, 100%, 100%, 31.6% and 63.9%, respectively. The sensitivity and accuracy of (18) F-FDG-PET/CT for the diagnosis of HCC recurrence were significantly higher than those of CEUS (P < 0.01, respectively). CONCLUSIONS Compared with CEUS, (18) F-FDG-PET/CT has higher sensitivity and accuracy in detecting the local recurrence of HCC after hepatectomy and/or RFA. It can be used to detect recurrent extrahepatic lesions of HCC effectively.
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Affiliation(s)
- Xiao Yan Wang
- Department of Nuclear Medicine, First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China
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Lim D, Lee SY, Lim KH, Chan CY. Hepatic adenoma mimicking a metastatic lesion on computed tomography-positron emission tomography scan. World J Gastroenterol 2013; 19:4432-4436. [PMID: 23885159 PMCID: PMC3718916 DOI: 10.3748/wjg.v19.i27.4432] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/02/2013] [Revised: 05/15/2013] [Accepted: 06/04/2013] [Indexed: 02/06/2023] Open
Abstract
Positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) is an imaging modality which reflects cellular glucose metabolism. Most malignant cells accumulate and trap 18F-FDG, allowing the visualisation of increased uptake. It is hence widely used to differentiate malignant from benign lesions. “False positive” findings of hepatic lesions have been described in certain instances such as hepatic abscesses, but are rare in cases involving hepatocellular adenomas. To our knowledge, there have been only 7 reports in the English literature documenting PET-avid hepatocellular adenomas; 6 of the 7 reports were published in the last 3 years with the first report by Patel et al. We report the case of a 44-year-old Chinese female patient with a history of cervical adenocarcinoma, referred for a hepatic lesion noted on a surveillance computed tomography (CT) scan. A subsequent CT-PET performed showed a hypermetabolic lesion (standardized uptake value 7.9) in segment IVb of the liver. After discussion at a multi-disciplinary hepato-pancreato-biliary conference, the consensus was that of a metastatic lesion from her previous cervical adenocarcinoma, and a resection of the hepatic lesion was performed. Histology revealed features consistent with a hepatocyte nuclear factor-1 α inactivated steatotic hepatocellular adenoma.
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Schierz JH, Opfermann T, Steenbeck J, Lopatta E, Settmacher U, Stallmach A, Marlowe RJ, Freesmeyer M. Early Dynamic 18F-FDG PET to Detect Hyperperfusion in Hepatocellular Carcinoma Liver Lesions. J Nucl Med 2013; 54:848-54. [PMID: 23528383 DOI: 10.2967/jnumed.112.113936] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Bilateral breast uptake demonstrated on FDG PET/CT scans in 3 male patients with hepatocellular carcinomas. Clin Nucl Med 2012; 37:520-1. [PMID: 22475911 DOI: 10.1097/rlu.0b013e31823ea993] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
We reported 3 male patients with hepatocellular carcinoma who underwent FDG PET/CT for systemic survey before liver transplantation. All of their scans demonstrated obvious FDG uptake in bilateral breasts. These uptakes might be owing to gynecomastia caused by an increase in free estrogen related to the cirrhotic liver.
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26
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Mazzio EA, Boukli N, Rivera N, Soliman KFA. Pericellular pH homeostasis is a primary function of the Warburg effect: inversion of metabolic systems to control lactate steady state in tumor cells. Cancer Sci 2012; 103:422-32. [PMID: 22320183 DOI: 10.1111/j.1349-7006.2012.02206.x] [Citation(s) in RCA: 47] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2011] [Revised: 11/22/2011] [Accepted: 12/08/2011] [Indexed: 12/25/2022] Open
Abstract
The Warburg effect describes a heightened propensity of tumor cells to produce lactic acid in the presence or absence of O(2) . A generally held notion is that the Warburg effect is related to energy. Using whole-genome, proteomic MALDI-TOF-MS and metabolite analysis, we investigated the Warburg effect in malignant neuroblastoma N2a cells. The findings show that the Warburg effect serves a functional role in regulating acidic pericellular pH (pHe), which is mediated by metabolic inversion or a fluctuating dominance between glycolytic-rate substrate level phosphorylation (SLP) and mitochondrial (mt) oxidative phosphorylation (OXPHOS) to control lactic acid production. The results also show that an alkaline pHe caused an elevation in SLP/OXPHOS ratio (approximately 98% SLP/OXPHOS); while the ratio was approximately 56% at neutral pHe and approximately 93% in acidic pHe. Acidic pHe paralleled greater expression of mitochondrial biogenesis and OXPHOS genes, such as complex III-V (Uqcr10, Atp5 and Cox7c), mt Fmc1, Romo1, Tmem 173, Tomm6, aldehyde dehydrogenase, mt Sod2 mt biogenesis component PPAR-γ co-activator 1 adjunct to loss of mt fission (Mff). Moreover, acidic pHe corresponded to metabolic efficiency evidenced by a rise in mTOR nutrient sensor GβL, its downstream target (Eif4ebp1), insulin modulators (Trib3 and Fetub) and loss of catabolic (Hadhb, Bdh1 and Pygl)/glycolytic processes (aldolase C, pyruvate kinase, Nampt and aldose-reductase). In contrast, alkaline pHe initiated loss of mitofusin 2, complex II-IV (Sdhaf1, Uqcrq, Cox4i2 and Aldh1l2), aconitase, mitochondrial carrier triple repeat 1 and mt biosynthetic (Coq2, Coq5 and Coq9). In conclusion, the Warburg effect might serve as a negative feedback loop that regulates the pHe toward a broad acidic range by altering lactic acid production through inversion of metabolic systems. These effects were independent of changes in O(2) concentration or glucose supply.
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Affiliation(s)
- Elizabeth A Mazzio
- College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, Florida, USA
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