© Springer International Publishing Switzerland 2015
Leonard Berliner and Heinz U. Lemke (eds.)An Information Technology Framework for Predictive, Preventive and Personalised MedicineAdvances in Predictive, Preventive and Personalised Medicine810.1007/978-3-319-12166-6_55. Imaging in Hepatocellular Carcinoma: PET/CT
(1)
Georgetown University Medical Center, Washington, DC, USA
Abstract
In the last two decades, the development of Positron Emission Tomography (PET), and then PET with Computed Tomography (PET/CT) imaging, has had a large impact on the management of a number of cancer types. PET/CT imaging benefits from the possibility of obtaining both structural (CT) and functional (PET) cancer information at the same time. PET obtains images of the biodistribution of radiopharmaceuticals that can be designed to target different biological processes. In current clinical cancer imaging, most PET imaging studies are performed using an analog of glucose, fluorodeoxyglucose (FDG), labeled with the radioactive Fluorine-18. Imaging with FDG is particularly useful because following malignant transformation, various tumors are characterized by increased glucose utilization that is reflected by increased uptake and accumulation of FDG. In oncology, PET imaging with FDG often provides more sensitive and more specific information about the extent of disease than morphologic/anatomic imaging alone. PET also offers an earlier and often better assessment of response to treatment and an overall better accuracy to restage disease after completion of a treatment course. This in turns results in an overall improved prognostic evaluation during and after treatment. Although the role of PET/CT is limited in patients with HCC, the current status of this imaging technology is reviewed.
Keywords
Personalized medicineHepatocellular carcinomaLiver metastasesDiagnosisImagingStagingComputed tomographyPositron emission tomographyFluorodeoxyglucose (FDG)Treatment evaluation5.1 Introduction
In the last two decades, the development of Positron Emission Tomography (PET) and then PET with Computed Tomography (PET/CT) imaging has had a large impact on the management of a number of cancer types. PET/CT imaging benefits from the possibility to obtain both structural (CT) and functional (PET) cancer information at the same time. PET obtains images of the biodistribution of radioactive labeled compounds (radiopharmaceuticals) that can be designed to target different biological processes.
5.1.1 Pharmacology
Several radiopharmaceuticals are available for PET that are able to image various aspects of cancer biology such as cell proliferation and DNA synthesis, tumor hypoxia, tumor angiogenesis, and cell apoptosis. However, in clinical cancer imaging, most of the PET imaging studies are performed using an analog of glucose, fluorodeoxyglucose (FDG), labeled with the radioactive Fluorine-18 (18F). Imaging with FDG is particularly useful because following malignant transformation, various tumors are characterized by an increased glucose utilization that is reflected by an increased uptake and accumulation of FDG. The uptake mechanism and biochemical pathway of FDG has been widely studied both in vitro and in vivo. The transport of the radiotracer through the cell membrane via glucose transport proteins, particularly glucose transporter type 1 (GLUT-1), and subsequent intracellular phosphorylation by hexokinase (HK) have been identified as key steps for subsequent tissue accumulation [1]. Because FDG-6-phosphate is not a suitable substrate for glucose-6-phosphate isomerase, and the enzyme level of glucose-6-phosphatase is generally low in tumors, FDG-6-phosphate accumulates in cells and is visualized by PET.
5.1.2 Role of PET Imaging in Oncology
5.1.2.1 Diagnosis
In oncology, PET imaging with FDG often provides more sensitive and more specific information about the extent of disease than morphologic/anatomic imaging alone. FDG-PET has become a standard imaging procedure for staging and restaging of many types of cancer [2]. The metabolic activity of neoplastic tissue measured by PET offers information about cancer biology and aggressiveness, and has proven to offer, in comparison to other imaging modalities and for most cancer types, an improved ability to differentiate benign from malignant lesions and therefore to identify early truly neoplastic disease. For example, a number of studies and a recent meta-analysis [3] of the available data have found that the addition of PET improves the accuracy of the diagnostic evaluation of single pulmonary nodules, reduces the number of indeterminate readings, and increases the inter- and intra-observer agreement on the presence of malignancy. FDG-PET imaging of cancer offers improved accuracy for the identification of lymph node and distant metastases and therefore provides better initial cancer staging.
5.1.2.2 Response to Treatment
When compared to other imaging modalities, PET offers also an earlier and often better assessment of response to treatment and an overall better accuracy to restage disease after completion of a treatment course. This in turns results in an overall improved prognostic evaluation during and after treatment. There is a large body of evidence on the importance of PET/CT in the assessment of the efficacy of treatment and on the prognostic value of the PET information coming from studies in patients with lymphomas [4]. There is no question that PET and PET/CT imaging has a significant impact on the clinical management of cancer patients. Data obtained from the National Oncologic PET Registry collected by Medicare has demonstrated that because of its greater accuracy, PET imaging significantly changed patient management in approximately 30 % of the cases [5].
There is also no doubt at this point that PET/CT imaging, by means of an overall improved anatomical and functional characterization of cancer, represents an important step towards an individualized, response-adapted treatment of cancer. Information regarding cancer biology, obtained from PET/CT imaging, is used to modify treatment based on the individual degree of response. In the future, the possibility of PET/CT to visualize multiple aspects of tumor biology besides glucose metabolism with FDG offers exciting new possibilities. It may be possible to plan individualized cancer treatments according to different biological cancer characteristics (such as tumor hypoxia for planning radiation treatment, estrogen receptors expression in breast cancer for planning hormonal therapy, and VEGF expression when planning anti-angiogenic treatments).
5.1.3 PET/CT in Guiding Ablation Therapies to the Liver
PET/CT imaging with FDG has been demonstrated to be useful in the clinical evaluation of patients being considered for local ablation therapies of primary and metastatic liver cancers. A number of studies have shown the value of PET/CT for the initial selection of patients being considered for local interventions, for the evaluation of response to local ablation treatment, as well as in the follow-up of these patients.
5.1.3.1 Metastatic Liver Disease
A recent paper on the role of PET/CT imaging in oncology [3] acknowledged that PET/CT has a better overall diagnostic accuracy for the evaluation of colorectal cancer and recommended that PET/CT be used in the initial disease staging, particularly for the evaluation of liver metastases. The same panel of experts recommended that PET/CT be used for the restaging and follow-up of these patients, to evaluate for local recurrence or to detect hepatic and extra-hepatic metastases.
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