Clinical applications of positron emission tomography in hepatic tumors

Fluorodeoxyglucose (FDG), which allows the evaluation of glucose metabolism, is widely used for tumor diagnosis using positron emission tomography (PET). FDG‐PET, which is used for the diagnosis of intrahepatic tumor lesions, shows high FDG accumulation in cholangiocellular carcinoma (CCC) and metastatic liver cancer. FDG‐PET shows high FDG accumulation in moderately or poorly differentiated hepatocellular carcinoma (HCC) and is useful for the diagnosis of extrahepatic HCC metastases and recurrences. However, because the imaging method frequently shows low FDG accumulation in well‐differentiated HCC, it is not very useful for that diagnosis. For the diagnosis of well‐differentiated HCC, F‐18 fluorocholine for evaluation of phospholipid metabolism and C‐11 acetate for evaluation of free fatty acid metabolism are useful in the diagnosis of that HCC. It is expected that the combination of these PET agents will enhance the diagnostic performance of FDG‐PET for HCC in the future. The problem of a lack of anatomical information is being resolved with the development of the use of PET in combination with computed tomography or magnetic resonance imaging. For the problem of low resolution, PET devices using semiconductors have been developed.     

Positron emission tomography/computed tomography with (18)F-fluorodeoxyglucose identifies tumor growth or thrombosis in the portal vein with hepatocellular carcinoma

Patients suffering from hepatocellular carcinoma (HCC) with tumor thrombus in the portal vein generally have a poor prognosis. Portal vein tumor thrombus must be distinguished from portal vein blood thrombus, and this identification plays a very important role in management of HCC. Conventional imaging modalities have limitations in discrimination of portal vein tumor thrombus. The application of positron emission tomography (PET) with 18F-fluorodeoxyglucose (18F-FDG) for discrimination between tumor extension and blood thrombus has been reported in few cases of HCC, while portal tumor thrombosis and portal vein clot identified by 18F-FDG PET/CT in HCC patients has not been reported so far. We present two HCC cases, one with portal vein tumor thrombus and one thrombosis who were identified with 18F-FDG PET/CT. This report illustrates the complimentary value of combining the morphological and functional imaging in achieving a correct diagnosis in such clinical situations.     

Diagnostic value for extrahepatic metastases of hepatocellular carcinoma in positron emission tomography/computed tomography scan

AIM: To evaluated the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan in diagnosis of hepatocellular carcinoma (HCC) and extrahepatic metastases.METHODS: A total of 138 patients with HCC who had both conventional imaging modalities and ¹⁸F-FDG PET/CT scan done between November 2006 and March 2011 were enrolled. Diagnostic value of each imaging modality for detection of extrahepatic metastases was evaluated. Clinical factors and tumor characteristics including PET imaging were analyzed as indicative factors for metastases by univariate and multivariate methods.RESULTS: The accuracy of chest CT was significantly superior compared with the accuracy of PET imaging for detecting lung metastases. The detection rate of metastatic pulmonary nodule ≥ 1 cm was 12/13 (92.3%), when < 1 cm was 2/10 (20%) in PET imaging. The accuracy of PET imaging was significantly superior compared with the accuracy of bone scan for detecting bone metastases. In multivariate analysis, increased tumor size (≥ 5 cm) (P = 0.042) and increased average standardized uptake value (SUV) uptake (P = 0.028) were predictive factors for extrahepatic metastases. Isometabolic HCC in PET imaging was inversely correlated in multivariate analysis (P = 0.035). According to the receiver operating characteristic curve, the optimal cutoff of average SUV to predict extrahepatic metastases was 3.4.CONCLUSION: ¹⁸F-FDG PET/CT scan is invaluable for detection of lung metastases larger than 1 cm and bone metastases. Primary HCC having larger than 5 cm and increased average SUV uptake more than 3.4 should be considered for extrahepatic metastases.     

Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management

Hepatocellular carcinoma （HCC） is one of the most common primary cancers in the world. Surgery is the gold standard for treatment of patients with HCC. Recurrence and metastasis are the major obstacles to further improve the prognosis of HCC. Most recurrences are intrahepatic. However, 30% of the recurrences are extrahepatic. The role of resection in intrahepatic recurrences is widely accepted. The role of resection in extrahepatic HCC recurrence and metastasis is not well established. 18F fluorodeoxyglucose （18F-FDG） positron emission tomography/computer tomography （PET/CT） is useful in detecting distant metastasis from a variety of malignancies and shows superior accuracy to conventional imaging modalities in identification of intrahepatic and extrahepatic metastasis. We present one patient with one new isolated omental lymph node metastasis, who had a history of huge HCC resected six years ago. The metastatic focus was identified with 18 F-FDG PET/CT and resected. The follow-up revealed good prognosis with a long-term survival potential after resection of the omental lymphatic metastasis.     

Molecular imaging and therapy targeting copper metabolism in hepatocellular carcinoma

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.     

Molecular imaging of plaques in coronary arteries with PET and SPECT

Coronary artery disease remains a major cause of mortality. Presence of atherosclerotic plaques in the coronary artery is responsible for lu-men stenosis which is often used as an indicator for determining the severity of coronary artery disease. However, the degree of coronary lumen stenosis is not often related to compromising myocardial blood flow, as most of the cardiac events that are caused by atherosclerotic plaques are the result of vulnerable plaques which are prone to rupture. Thus, identification of vulnerable plaques in coronary arteries has become increas-ingly important to assist identify patients with high cardiovascular risks. Molecular imaging with use of positron emission tomography （PET） and single photon emission computed tomography （SPECT） has fulfilled this goal by providing functional information about plaque activity which enables accurate assessment of plaque stability. This review article provides an overview of diagnostic applications of molecular imaging tech-niques in the detection of plaques in coronary arteries with PET and SPECT. New radiopharmaceuticals used in the molecular imaging of coro-nary plaques and diagnostic applications of integrated PET/CT and PET/MRI in coronary plaques are also discussed.     

Metabolic imaging for guidance of curative treatment of isolated pelvic implantation metastasis after resection of spontaneously ruptured hepatocellular carcinoma: A case report

Spontaneous rupture of hepatocellular carcinoma (HCC) is a life-threatening complication and its prognosis is significantly poor because of the high recurrence rate after initial hepatectomy. Resection of isolated extrahepatic metastasis of HCC has been advocated to obtain a possibility of long-term survival. However, it is a challenge for clinicians to detect implantation metastasis of spontaneously ruptured HCC. Accurate re-staging plays the most important role in making a decision on isolated metastasis resection. ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography/computed tomography (PET/CT) is useful in detecting intra-abdominal implantation metastasis from a variety of malignancies and shows superior accuracy to conventional imaging modalities in determining the location of metastasis. We present one patient with a new isolated pelvic implantation metastasis detected by ¹⁸F-FDG PET/CT and pathologically confirmed by PET/CT-guided percutaneous biopsy, who had a history of resection of spontaneously ruptured HCC two years ago. The patient’s condition was stable at the 6-mo follow-up after resection of the isolated pelvic metastasis.     

Multimodality imaging in coronary artery disease – “The more the better?”

Multimodality imaging in coronary artery disease (CAD) comprises a combination of information from more than one imaging technique. These combinations, performed in a side-by-side or fusion mode, include computed tomography (CT) and single photon emission computed tomography (SPECT), positron emission tomography (PET) and CT, and PET with magnetic resonance imaging (MRI). Data thus obtained lead to either a summative or synergistic gain of information. For instance, morphology (coronary plaques/stenosis) can be depicted by coronary CT angiography, whereas functional aspects of CAD such as myocardial perfusion abnormalities or myocardial metabolism can be evaluated by the complementary technique in order to separate a hemodynamic significant coronary stenosis from a hemodynamic non-significant stenosis. Distinguishing these two entities has an important impact on patient management. Beyond the diagnostic yield, some of these combinations in multimodality imaging also have prognostic implications. In this article, we will describe different multimodality imaging approaches (CT/SPECT, PET/CT and PET/MRI) for evaluation of CAD in patients with suspected or known CAD and put them into the context of current knowledge.     

The role of imaging techniques in the management of multiple myeloma

Bone disease is the major feature of multiple myeloma (MM). Imaging is required for correct staging, in the follow‐up after treatment and, as recently highlighted, is predictor of prognosis. In the near future, whole‐body X‐Ray may be replaced by more sensitive techniques, such as whole‐body low‐dose computerized tomography (CT). Magnetic resonance imaging (MRI) is the gold standard method for assessing bone marrow infiltration of the spine, predicting the risk of vertebral fracture and distinguishing between benign and malignant osteoporosis. Positron emission tomography (PET) with CT (PET/CT) provides important information about the extent of whole‐body disease, including soft tissue masses, and is the best tool to distinguish between active or inactive disease after therapy. Both MRI and PET/CT are predictors of clinical outcome. A prospective use of these newer imaging techniques in both clinical trials and clinical practice may help optimize MM management in the near future.     

Emerging role of ~(18)F-fluorodeoxyglucose positron emission tomography for guiding management of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is one of major causes of cancer mortality worldwide. For decades, ~(18)F-fluorodeoxyglucose(FDG) positron emission tomography(PET) has been widely used for staging, predicting prognosis, and detecting cancer recurrence in various types of malignant diseases. Due to low sensitivity of FDG PET for detecting intrahepatic HCC lesions, the clinical value of FDG PET in HCC patients has been limited. However, recent studies with diverse analytic methods have shown that FDG PET has promising role in aiding management of HCC patients. In this review, we will discuss the clinical role of FDG PET for staging, predicting prognosis, and evaluating treatment response in HCC. Further, we will focus on recent clinical studies regarding implication of volumetric FDG PET parameters, the significance of FDG uptake in HCC for selecting treatment and predicting treatment response, and the use of radiomics of FDG PET in HCC.     

Efficacy of 3D‐positron emission tomography/computed tomography for upper abdomen

Recent advancement in computed tomography (CT) enables us to obtain high spatial resolution image and made it possible to construct extensive high‐definition three‐dimensional (3D) images. But a lack of contrast resolution in CT alone is still remained problem. Meanwhile, as fluorodeoxyglucose‐positron emission tomography (PET) can visualize tumors in high contrast, we can create 3D images fusing the accumulation in tumors on PET/CT images. Such images can play the role of a “map of body” which makes it easy to understand the anatomical information before surgery. We also try to evaluate segmental liver function by using PET/CT fusion images. By using ¹¹C‐methionine PET/contrast‐enhanced CT, superior image quality compared to single photon emission computed tomography/CT can be obtained. CT, especially with contrast enhancement for obtaining anatomical imaging information plus PET for obtaining functional imaging information is a highly compatible combination, and adding these two types information will further increase clinical usefulness.     

Positron emission tomography (PET) for cholangiocarcinoma

The combination of positron emission tomography (PET) with computed tomography (PET-CT) provides simultaneous metabolic and anatomic information on tumors in the same imaging session. Sensitivity of PET/PET-CT is higher for intrahepatic (>90%) than for extrahepatic cholangiocarcinoma (CCA) (about 60%). The detection rate of distant metastasis is 100%. PET, and particularly PET-CT, improves the results and impacts on the oncological management in CCA compared with other imaging modalities. Therefore, PET-CT is recommended in the preoperative staging of intrahepatic (strength of recommendation: moderate) and extrahepatic (strength of recommendation: low) CCA.     

Surveillance of patients after initial treatment of ovarian cancer

The surveillance of ovarian cancer patients after initial treatment is a challenging question in clinical practice. Serum CA 125 assay, physical examination, and imaging examinations have been employed with different time schedules for the follow-up of asymptomatic patients. Rising serum CA 125 levels may precede the clinical detection of relapse in 56-94% of cases with a median lead time of 3-5 months. An ongoing randomised phase III European trial is comparing the benefits of early administration of chemotherapy based on serum CA 125 assay alone versus delaying treatment until clinical or radiological detection of recurrent disease. Physical examination, with or without ultrasound, is very useful for the surveillance of these patients, since approximately 25-50% of relapses involve the pelvis. Additional radiological imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), are usually performed in asymptomatic patients with rising CA 125 levels as well as in patients with suspicious symptoms or signs. Integrated positron emission tomography (PET) and CT scanners (PET/CT) can identify recurrent disease in tissues that appear normal at CT imaging as well as metastatic lesions intimately associated with the bowel wall that are difficult to detect with CT or MRI, so that in most series PET/CT has a higher diagnostic reliability than that of conventional imaging techniques. Moreover, PET/CT can disclose unusual supra-diaphragmatic spreading of the disease and may be very helpful for treatment planning, especially for the selection of patients suitable for secondary surgical cytoreduction. A prospective, randomised trial of therapeutic interventions based on stratification by PET/CT disease status could elucidate the real impact of this diagnostic procedure in the management of patients with recurrent ovarian cancer.     

Advanced imaging techniques in the therapeutic response of transarterial chemoembolization for hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the major causes of morbidity and mortality in patients with chronic liver disease. Transarterial chemoembolization (TACE) can significantly improve the survival rate of patients with HCC and is the first treatment choice for patients who are not suitable for surgical resections. The evaluation of the response to TACE treatment affects not only the assessment of the therapy efficacy but also the development of the next step in the treatment plan. The use of imaging to examine changes in tumor volume to assess the response of solid tumors to treatment has been controversial. In recent years, the emergence of new imaging technology has made it possible to observe the response of tumors to treatment prior to any morphological changes. In this article, the advances in studies reporting the use of computed tomography perfusion imaging, diffusion-weighted magnetic resonance imaging (MRI), intravoxel incoherent motion, diffusion kurtosis imaging, magnetic resonance spectroscopy, magnetic resonance perfusion-weighted imaging, blood oxygen level-dependent MRI, positron emission tomography (PET)/computed tomography and PET/MRI to assess the TACE treatment response are reviewed.     

Metabolic restaging of hepatocellular carcinoma using whole-body 18F-FDG PET/CT

AIM: To evaluate the ability of ¹⁸F-fluorodeoxyglucose positron emission and computed tomography (¹⁸F-FDG PET/CT) in restaging of hepatocellular carcinoma (HCC) after treatment.METHODS: We reviewed a database of the diagnostic performance of ¹⁸F-FDG PET/CT scan for patients with HCC following local or regional treatment. The database consisted of ¹⁸F-FDG PET/CT information of 21 male and 4 female (age range, 27-81 years; mean age, 51.6 years) patients who had received surgical resection and/or interventional treatments and then underwent ¹⁸F-FDG PET/CT scan. All patients had received enhanced CT scan of the liver two weeks before or after the ¹⁸F-FDG PET/CT scan. Intrahepatic recurrence and/or extrahepatic metastases were confirmed by histological analysis or clinical and imaging follow-up. The accuracy of ¹⁸F-FDG PET/CT study was determined by histopathological results or by clinical and imaging follow-up.RESULTS: ¹⁸F-FDG PET/CT was abnormal in 19 of the 25 (76.0%) patients. In detecting HCC recurrence, ¹⁸F-FDG PET/CT scored 17 true positives, 5 true negatives, 2 false positives and 1 false negative. The sensitivity, specificity and accuracy of ¹⁸F-FDG PET/CT in detecting HCC recurrence was 89.5%, 83.3% and 88%, respectively. ¹⁸F-FDG PET/CT had an impact on management of these patients by settling the problem of an unexplained increase in alpha-fetoprotein after treatment (14 patients), by monitoring response to the treatment and guiding additional regional therapy (12 patients), by identifying extrahepatic metastases (10 patients), by identifying tumor growth or thrombosis in the portal vein (6 patients), or by guiding surgical resection of extrahepatic metastases (2 patients).CONCLUSION: Our results suggest that whole body ¹⁸F-FDG PET/CT may be useful in the early evaluation of residual, intrahepatic recurrent or extrahepatic metastatic lesions and able to provide valuable information for the management of HCC recurrence.     

Comparison of (11)C-acetate positron emission tomography and (67)Gallium citrate scintigraphy in patients with hepatocellular carcinoma.

AIMS: Nuclear imaging may have an increasing role in the diagnosis of hepatocellular carcinoma (HCC). The aim of this study was to compare prospectively the Gallium-67 citrate ((67)Ga) scintigraphy results with those obtained by positron emission tomography (PET) using (11)C-acetate in patients with HCC. METHODS: We prospectively analysed 21 patients (mean age, 64+/-11 years) with histopathologically verified HCC undergoing (11)C-acetate PET and (67)Ga scintigraphy. (67)Ga scans were not performed in three of these 21 patients due to the exacerbation of the disease. Whole-body (11)C-acetate PET were performed following intravenous injection of 850 MBq of (11)C-acetate. For (67)Ga scintigraphy, whole-body, planar and single photon emission computed tomography imaging acquisitions were performed after intravenous application of a mean dose of 189 MBq (67)Ga. RESULTS: (67)Ga scintigraphy found abnormalities only in 10 of 18 patients (56%) and detected 22 of 46 clinically involved sites (48%); it was false-positive in two patients. (11)C-acetate PET found abnormalities in 14 of 18 patients (78%) and detected 36 of 46 clinical lesions (78%); it was false-positive in one patients. In one patient with left supraclavicular lymph node metastases, neither the (67)Ga scintigraphy nor the conventional computed tomography have shown the lesions, which were clearly demonstrated by the (11)C-acetate PET. CONCLUSION: Our results indicate significantly higher sensitivity and specificity of (11)C-acetate PET than (67)Ga scan in detection of HCC lesions. This study suggests that imaging with (11)C-acetate PET might play a potential role in the diagnostic workup of patients with HCC.     

Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis

Hepatocellular carcinoma(HCC) is the most common primary liver cancer and a major public health problem worldwide. Hepatocarcinogenesis is a complex multistep process at molecular, cellular, and histologic levels with key alterations that can be revealed by noninvasive imaging modalities. Therefore, imaging techniques play pivotal roles in the detection, characterization, staging, surveillance, and prognosis evaluation of HCC. Currently, ultrasound is the first-line imaging modality for screening and surveillance purposes. While based on conclusive enhancement patterns comprising arterial phase hyperenhancement and portal venous and/or delayed phase wash-out, contrast enhanced dynamic computed tomography and magnetic resonance imaging(MRI) are the diagnostic tools for HCC without requirements for histopathologic confirmation. Functional MRI techniques, including diffusion-weighted imaging, MRI with hepatobiliary contrast agents, perfusion imaging, and magnetic resonance elastography, show promise in providing further important information regarding tumor biological behaviors. In addition, evaluation of tumor imaging characteristics, including nodule size, margin, number, vascular invasion, and growth patterns, allows preoperative prediction of tumor microvascular invasion and patient prognosis. Therefore, the aim of this article is to review the current state-of-the-art and recent advances in the comprehensive noninvasive imaging evaluation of HCC. We also provide the basic key concepts of HCC development and an overview of the current practice guidelines.     

Thoracic positron emission tomography: 18F-fluorodeoxyglucose and beyond

Ongoing technologic and therapeutic advancements in medicine are now testing the limits of conventional anatomic imaging techniques. The ability to image physiology, rather than simply anatomy, is critical in the management of multiple disease processes, especially in oncology. Nuclear medicine has assumed a leading role in detecting, diagnosing, staging and assessing treatment response of various pathologic entities, and appears well positioned to do so into the future. When combined with computed tomography (CT) or magnetic resonance imaging (MRI), positron emission tomography (PET) has become the sine quo non technique of evaluating most solid tumors especially in the thorax. PET/CT serves as a key imaging modality in the initial evaluation of pulmonary nodules, often obviating the need for more invasive testing. PET/CT is essential to staging and restaging in bronchogenic carcinoma and offers key physiologic information with regard to treatment response. A more recent development, PET/MRI, shows promise in several specific lung cancer applications as well. Additional recent advancements in the field have allowed PET to expand beyond imaging with ¹⁸F-flurodeoxyglucose (FDG) alone, now with the ability to specifically image certain types of cell surface receptors. In the thorax this predominantly includes ⁶⁸Ga-DOTATATE which targets the somatostatin receptors abundantly expressed in neuroendocrine tumors, including bronchial carcinoid. This receptor targeted imaging technique permits targeting these tumors with therapeutic analogues such as ¹⁷⁷Lu labeled DOTATATE. Overall, the proper utilization of PET in the thorax has the ability to directly impact and improve patient care.     

Metabolic imaging using F18-fluorodeoxyglucose to assess myocardial viability

Over the past 10 years, F18-fluorodeoxyglucose (FDG) imaging with positron emission tomography (PET) has emerged as an important technique in the delineation of myocardial viability. Using this technique it has become possible to predict recovery of ventricular function after revascularization in patients with chronic coronary artery disease. Data from long-term (although retrospective) follow-up studies have demonstrated that patients with viable myocardium on FDG PET who do not undergo revascularization are prone to cardiac events, including cardiac death and non-fatal infarction. The same studies have pointed out that patients with viable tissue on FDG PET, who do undergo revascularization, improve substantially in symptoms related to congestive heart failure. To allow FDG imaging in centers without PET equipment, recent studies have evaluated the use of FDG imaging with single photon emission computed tomography (SPECT) and 511 keV collimators. Preliminary data using this alternative approach are promising, but need further confirmation. In this review the experience with FDG imaging (using either PET or SPECT) in the assessment of tissue viability in patients with coronary artery disease will be discussed.     

Is endoscopic ultrasonography still the modality of choice in preoperative staging of gastric cancer?

The treatment option for gastric cancer is usually based on preoperative staging by imaging modalities. Endoscopic ultrasonography (EUS) and computed tomography (CT) have been used as the diagnostic modality of choice in preoperative staging of gastric cancer. Magnetic resonance imaging (MRI) has been employed in several studies, and (¹⁸F) 2-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) has emerged as a new promising imaging modality. The purpose of this article is to provide summarized information on preoperative staging using EUS, multi-detector row CT (MDCT), MRI and PET for gastric cancer. In T staging, both EUS and MDCT show high accuracy. MRI seemed to have better performance, but the number of MRI studies is limited. FDG-PET is not able to properly evaluate the depth of invasion. In N staging, the diagnostic accuracy of EUS, MDCT and MRI is not sufficient. In preoperative M staging, MDCT and FDG-PET showed similar diagnostic accuracies. FDG-PET/CT fusion could be expected to show better performance in the future. Physicians should keep in mind that each diagnostic modality has advantages and limitations and choose an appropriate diagnostic strategy tailored for each patient.