The value of positron emission tomography in the clinical evaluation of dementia

Positron emission tomography (PET) has been promoted as a means of improving the diagnosis of Alzheimer's disease (AD), but the evidence to support its incremental value is unclear. To assess the evidence regarding the use of PET in the clinical evaluation of AD, a systematic review of the English-language literature indexed in MEDLINE (1975-January 2001), the Cochrane Library (issue 4, 2000), and health technology assessment (HTA) reports was conducted. Articles identified by this review process were graded for methodological and reporting quality using a standardized grading scheme. Sixteen original articles and seven HTA reports were identified. In general, the articles addressed: using PET to differentiate AD from normal aging or non-Alzheimer's dementias, PET imaging compared with single positron emission computed tomography imaging, using PET to predict the progression of dementia, and agreement and reliability in the interpretation of PET images. Serious problems with study design and methodology in all articles were identified. Previous HTA reports have generally recommended that PET not be used in the clinical evaluation of dementia. In conclusion, there is little evidence to support the addition of PET to the routine clinical evaluation of patients with suspected or established dementia. Suggestions for future research in this area are offered.     

Molecular imaging of gastroenteropancreatic neuroendocrine tumors

Somatostatin-receptor scintigraphy has become an obligatory molecular imaging method in the management of patients with neuroendocrine tumors when metastatic disease is suspected. Using positron emission tomography and new somatostatin analogues, sensitivity of somatostatin receptor imaging has further increased. With a combination of morphologic imaging methods, such as hybrid imaging by PET/CT, this method represents the method of choice in many centers and efforts are under way to translate somatostatin receptor imaging onto a cellular level by endoscopic confocal microscopy. Other clinically relevant functional pathways in neuroendocrine tumors that are accessible by PET imaging are glucose metabolism and amine precursor uptake and decarboxylation.     

Whole-body (11)C-5-hydroxytryptophan positron emission tomography as a universal imaging technique for neuroendocrine tumors: comparison with somatostatin receptor scintigraphy and computed tomography

Neuroendocrine tumors (NETs) can be small and situated almost anywhere throughout the body. Our objective was to investigate whether whole-body (WB) positron emission tomography (PET) with (11)C-5-hydroxytryptophan (5-HTP) can be used as a universal imaging technique for NETs and to compare this technique with established imaging methods. Forty-two consecutive patients with evidence of NET and a detected lesion on any conventional imaging (six bronchial, two foregut, 16 midgut, and two thymic carcinoids; one ectopic Cushing's syndrome; four gastrinomas; one insulinoma; six nonfunctioning endocrine pancreatic tumors; one gastric carcinoid, one paraganglioma; and two endocrine-differentiated pancreatic carcinomas) were studied. The WB-(11)C-5-HTP-PET examinations were compared with WB-computed tomography (CT) and somatostatin receptor scintigraphy (SRS). Tumor lesions were imaged with PET in 95% of the patients. In 58% of the patients, PET could detect more lesions than SRS and CT and equal numbers in 34%, whereas in three cases, SRS or CT showed more lesions. In 84% (16 of 19 patients), PET could visualize the primary tumor compared with 47 and 42% for SRS and CT, respectively. The surgically removed PET-positive primary tumor sizes were 6-30 mm. To conclude, this study indicates that WB-(11)C-5-HTP-PET can be used as a universal imaging method for detection of NETs. This study also shows that WB-(11)C-HTP-PET is sensitive in imaging small NET lesions, such as primary tumors, and can in a majority of cases image significantly more tumor lesions than SRS and CT.     

Whole-body positron emission tomography using 18F-fluorodeoxyglucose for initial staging of patients with Hodgkin's disease

An accurate initial staging of patients with Hodgkin's disease (HD) is important for the evaluation of clinical stage and risk factors, which are crucial for the choice of an appropriate treatment. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is useful for detecting active tumor tissue in patients with lymphoproliferative diseases and may contribute to conventional staging methods in patients with HD. Twenty-two patients who presented with newly diagnosed HD underwent conventional staging methods including computed tomography (CT) as well as FDG PET. Lesions apparent in FDG PET and CT were correlated to each other. Seventy-seven lesions were observed either in PET or CT or in both. In 48 (62%) lesions PET and CT were both positive. In 20 (26%) sites, PET was positive and CT negative. Of 22 patients (18%) 4 were upstaged due to these positive PET findings, and as a result one patient received a different therapeutic regimen. PET failed to detect nine (12%) CT-positive sites in six patients. Statistically, these data are reflected by a sensitivity for PET and CT of 88% and 74%, respectively. Specificity of both imaging modalities was 100%. PET can contribute valuable information as an additional staging examination and led to an upstaging in some patients with primary HD. However, PET should not be used as the only imaging modality as it failed to detect CT-positive, active tumor regions in some cases.     

Impact of pre-operative positron emission tomography in gallbladder cancer

Background

Current pre-operative staging methods for gallbladder cancer (GBC) are suboptimal in detecting metastatic disease. Positron emission tomography (PET) may have a role but data are lacking.

Methods

Patients with GBC and PET assessed by a hepatobiliary surgeon in clinic between January 2001 and June 2013 were retrospectively reviewed. Computed tomography (CT)/magnetic resonace imaging (MRI) were correlated with PET scans and analysed for evidence of metastatic or locally unresectable disease. Medical records were reviewed to determine if PET scanning was helpful by preventing non-therapeutic surgery or enabling resection in patients initially deemed unresectable.

Results

There were 100 patients including 63 incidental GBC. Thirty-eight patients did not proceed to surgery, 35 were resected and 27 patients were explored but had unresectable disease. PET was positive for metastatic disease in 39 patients (sensitivity 56%, specificity 94%). Five patients definitively benefitted from PET: in 3 patients PET found disease not seen on CT, and 2 patients with suspicious CT findings had negative PET and successful resections. In a further 12 patients PET confirmed equivocal CT findings. Three patients had additional invasive procedures performed owing to PET avidity in other sites. Utility of PET was higher in patients with suspicious nodal disease on CT [odds ratio (OR) 7.1 versus no nodal disease, P = 0.0004], and in patients without a prior cholecystectomy (OR 3.1 versus post-cholecystectomy, P = 0.04).

Conclusion

Addition of PET to conventional cross-sectional imaging has a modest impact on management pre-operatively particularly in patients without a prior cholecystectomy and to confirm suspicious nodal disease on CT.     

Staging in oesophageal cancer

Accurate staging defines groups for stage-specific treatment, minimising inappropriate treatment. Application of dedicated staging methods - including 16-64 multidetector computed tomography (CT), endoscopic ultrasonography with fine-needle aspiration (EUS-FNA) and positron emission tomography (PET) - results in better staging of oesophageal cancer. PET as a metabolic imaging technique that is usually applied after (or recently in combination with) CT (PET/CT) improves the accuracy of non-invasive staging, especially in locally advanced oesophageal cancer patients. Whether EUS-FNA or PET/CT should be performed as a first diagnostic step is still a matter of debate. Fluoro-2-deoxyglucose (FDG) PET is also promising tool in assessing neoadjuvant treatment response. Application of these dedicated staging methods has a learning curve, suggesting a prominent role for centralisation.     

Role of positron emission tomography in determining the extent of CNS ischemia in patients with sickle cell disease

Nearly 25% of patients with sickle cell disease (SCD) experience central nervous system morbidity involving both large and small vessel disease. Optimal imaging methods for determining the extent of ischemia are not known. Positron emission tomography (PET) has the unique ability to show tissue function as well as structure. Reports concerning patients with non-SCD neurodegenerative disorders suggest PET may be useful in determining prognosis. We compared magnetic resonance imaging, magnetic resonance angiography, and neuropsychological testing with PET prospectively. Six patients with SCD and a history of stroke, aged 10 to 28, were enrolled. PET studies were performed on an ECAT HR 47 scanner (Siemens/CTI, Knoxville, TN) using 18-F-fluorodeoxyglucose as a tracer. PET interpretations were conducted in blinded fashion. MRI studies found two patients with only small vessel disease and four with both large and small vessel disease. In two of four subjects with large vessel disease, PET showed a corresponding metabolic abnormality and also identified an area of hypometabolism extending beyond the anatomical lesion as shown by MRI. PET did not demonstrate an abnormality corresponding with small vessel disease. Detailed neuropsychological testing demonstrated cognitive dysfunction in all cases. For some patients, PET may add sensitivity in detecting impaired metabolism in the area surrounding a major vessel infarct. However, the technique does not appear to be generally useful in characterizing small watershed or deep white matter infarcts. Larger studies, to include control subjects and carefully selected untransfused SCD patients, are needed. A combination of conventional imaging and neuropsychological testing remains the preferred evaluation for most SCD patients with neurologic symptoms.     

Functional imaging in predicting response to antineoplastic agents and molecular targeted therapies in lung cancer: a review of existing evidence

The increasing use of FDG-PET ((18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography) imaging in the staging of non-small-cell lung cancer (NSCLC) may result in a significant shift in stage distribution, with an increased percentage of patients staged as having metastatic disease and consequently a higher percentage of patients treated with systemic therapy. The amount of FDG-PET uptake in primary lung lesions has been shown to be correlated with tumour growth rate. Data suggest that tumours with increased glucose uptake are presumably more metabolically active and more biologically aggressive, and standardized uptake value (SUV) at PET may be regarded as a prognostic factor. Growing evidence suggests that PET may be used as a predictive marker to assess the activity of antineoplastic agents, allowing close monitoring of the efficacy of the treatment in order to be able to switch earlier to alternative therapies according to the individual chemosensitivity of the tumour. Currently the value of FDG-PET for monitoring response is complicated by the heterogeneity of the published data on the methods used for FDG quantification and the selection of the primary targets and clinical endpoints. As a result, objective validation of proposed thresholds of responsiveness is lacking. This article discusses the assessment of treatment response in NSCLC patients using functional imaging, and emphasizes advantages and limitations in clinical management.     

Guidelines for the use of imaging in the management of patients with myeloma

The role of imaging in myeloma has gained increasing importance over the past few years. The recently revised definition of myeloma from the International Myeloma Working Group (IMWG) includes cross sectional imaging as a method to define bone disease and also incorporates its use in the disease definition for patients with suspected smouldering myeloma. The National Institute for Health and Care Excellence myeloma guidelines also recommend cross sectional imaging for patients with suspected myeloma. There is also increasing use of imaging in disease assessments and the International Myeloma Working Group has recently incorporated imaging in defining new response categories of minimal residual disease negativity, with or without imaging‐based evidence of disease. Plain X‐rays have previously been the standard imaging modality included in a myeloma work up at presentation but evidence is mounting for use of cross‐sectional modalities such as computed tomography (CT), magnetic resonance imaging (MRI) and ¹⁸fluoro‐deoxyglucose (¹⁸F‐FDG) positron emission tomography (PET)/CT. Funding and therefore availability of newer imaging techniques remains a barrier. Here, we propose an evidence‐based approach to the use and technical application of the latest imaging modalities at diagnosis and in the follow‐up of patients with myeloma and plasmacytoma.     

PET/CT imaging of lung cancer

Fluoro-deoxyglucose positron emission tomography (PET) imaging has a diagnostic and prognostic value in the initial staging, restaging, and surveillance of non-small-cell lung cancer (NSCLC). When used in conjunction with conventional radiologic imaging, PET imaging has been shown to result in significant changes in clinical management of NSCLC. Specifically, baseline PET imaging can improve initial staging and guide surgical and radiotherapy planning, whereas repeat PET imaging after the initiation of chemoradiotherapy can predict tumor response and help tailor therapy. After the end of definitive treatment, PET has greater diagnostic accuracy than other imaging modalities for the detection of tumor recurrence. The recent development of fused PET/CT imaging has improved the radiologic evaluation of NSCLC patients by combining metabolic and anatomic imaging; however, this has resulted in more complexity in the image interpretation. It is important for the interpreting physician to understand the role PET/CT plays in the staging, assessment of treatment, and follow-up after therapy in the multidisciplinary management of patients with NSCLC.     

Seeking a home for a PET, part 2: Defining the appropriate place for positron emission tomography imaging in the staging of patients with suspected lung cancer

In patients who have a high likelihood of having lung cancer, there is little role for positron emission tomography (PET) imaging for diagnosis of the primary lesion. The primary impact of PET imaging is in extrathoracic staging, but it should not replace a clinical evaluation by a physician experienced in lung cancer. PET imaging is most useful for confirmation of the presumed extrathoracic stage in patients with intermediate stages of lung cancer. The role of PET imaging is limited in patients with strong clinical signs of metastatic disease, or in patients with a clinical stage I lung cancer and a negative clinical evaluation. With regard to intrathoracic staging, PET imaging has a definite role in communities in which mediastinoscopy is not available, whereas the impact is limited in institutions in which invasive mediastinal staging is available. The data suggest that a positive PET result in the mediastinum should be confirmed by biopsy. A mediastinoscopy is also reasonable in patients with clinical stage III lung cancer who have no mediastinal PET uptake. It is unclear and controversial whether a biopsy is needed in patients with clinical stage II lung cancer who have no PET uptake in the mediastinum.     

Quantificação do fluxo sanguíneo miocárdico por tomografia por emissão de positrões – Atualização

Cardiovascular disease is the leading cause of death worldwide and ischemic heart disease is the most frequent etiology, with high economic costs for both treatment and diagnosis. Over the past two decades, the assessment of patients with this disease has undergone various changes, with cardiac positron emission tomography (PET) emerging as a powerful and versatile imaging exam for diagnosis and risk stratification of these patients. This review aimed to assess the utility of this exam, particularly through quantification of myocardial blood flow and myocardial flow reserve in the diagnosis and risk stratification of coronary artery disease. Compared to other imaging methods, measurement of these parameters by cardiac PET provides a better characterization of coronary artery disease, with particular value in microvascular and balanced multivessel disease.     

Usefulness of whole-body fluorine-18-fluorodeoxyglucose positron emission tomography in patients with large-vessel vasculitis: a systematic review

The objective of this study is to systematically review the role of positron emission tomography (PET) and PET/computed tomography (PET/CT) with fluorine-18-fluorodeoxyglucose (FDG) in patients with large-vessel vasculitis (LVV). A comprehensive literature search of published studies through April 2011 in PubMed/MEDLINE and Scopus databases regarding whole-body FDG-PET and PET/CT in patients with LVV was performed. We identified 32 studies including 604 LVV patients. The main findings of these studies are presented. The conclusions are the following: (1) FDG-PET and PET/CT are useful imaging methods in the initial diagnosis and in the assessment of activity and extent of disease in patients with LVV; (2) the correlation between FDG-PET findings and serological levels of inflammatory markers, as well as the usefulness of FDG-PET and PET/CT in evaluating treatment response, remains unclear; (3) it appears that there is a superiority of FDG-PET and PET/CT over conventional imaging methods in the diagnosis of LVV, but not in assessing disease activity under immunosuppressive treatment, in predicting relapse or in evaluating vascular complications; and (4) given the heterogeneity between studies with regard to PET analysis and diagnostic criteria, a standardization of the technique is needed.     

Nuclear perfusion imaging for functional evaluation of patients with known or suspected coronary artery disease: the future is now

Nuclear imaging, with both single-photon emission computed tomography and PET, has a well-established role in the assessment of patients with known or suspected coronary artery disease. There is a large body of evidence regarding the diagnostic accuracy and prognostic value of these modalities, however, they continue to evolve rapidly with advances in camera and tracer technology, as well as changes in imaging protocols to increase lab efficiency, improve image quality and to decrease radiation exposure to patients. Nuclear imaging also provides insights into atherogenesis at a molecular level and can be combined with other imaging modalities, providing both functional and structural data and complimentary information on the presence of coronary disease and its functional implications.     

18F-FDG PET/CT显像判断乳腺癌复发及转移的价值

目的探讨^18F-FDG PET/CT显像判断乳腺癌复发和转移的临床价值.方法28例手术治疗后临床疑有肿瘤复发或转移的乳腺癌患者均进行^18F-FDG PET/CT全身显像,应用目测法和半定量分析法判断结果（标准摄取值,SUV）.结果病理、活检、细胞学检查等证实17例有局部复发和（或）转移,^18F-FDG PET/CT显像正确诊断16例,检测灵敏度、特异性（94.12%,90.91%）明显高于传统影像学方法;在62个肿瘤复发和（或）转移灶中,PET/CT及常规影像学检查检出率分别为91.94%（57/62）、72.58%（45/62）,P＜0.05.结论^18F-FDG PET/CT显像是早期诊断乳腺癌复发和（或）转移良好的、无创性方法.     

Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis

Gallium-68 somatostatin receptor (SMSR) positron emission tomography (PET) and positron emission tomography/computed tomography (PET/CT) are valuable diagnostic tools for patients with neuroendocrine tumours (NETs). To date, a meta-analysis about the diagnostic accuracy of these imaging methods is lacking. Aim of our study is to meta-analyse published data about the diagnostic performance of SMSR PET or PET/CT in patients with thoracic and/or gastroenteropancreatic (GEP) NETs. A comprehensive computer literature search of studies published in PubMed/MEDLINE, Scopus and Embase databases through October 2011 and regarding SMSR PET or PET/CT in patients with NETs was carried out. Only studies in which SMSR PET or PET/CT were performed in patients with thoracic and/or GEP NETs were selected (medullary thyroid tumours and neural crest derived tumours were excluded from the analysis). Pooled sensitivity, pooled specificity and area under the ROC curve were calculated to measure the diagnostic accuracy of SMSR PET and PET/CT in NETs. Results: Sixteen studies comprising 567 patients were included in this meta-analysis. The pooled sensitivity and specificity of SMSR PET or PET/CT in detecting NETs were 93% (95% confidence interval [95% CI]: 91-95%) and 91% (95% CI: 82-97%), respectively, on a per patient-based analysis. The area under the ROC curve was 0.96. In patients with suspicious thoracic and/or GEP NETs, SMSR PET and PET/CT demonstrated high sensitivity and specificity. These accurate techniques should be considered as first-line diagnostic imaging methods in patients with suspicious thoracic and/or GEP NETs.     

Die Wertigkeit der Positronenemissionstomographie (PET) in der Nachsorge des Rektumkarzinoms

Aim: The aim of this study was the assessment of positron-emission tomography (PET) with 18F-fluordesoxyglucose as a diagnostic tool in the follow-up of patients after resection of rectal carcinomas.Patients and Methods: 36 patients suspicious of tumor recurrence in the follow-up after primary R0-resection of a rectal carcinoma underwent a PET investigation. Indications for PET were rising CEA values, positive morphological imaging or doubtful clinical investigation. Histopathological results in case of reoperation, or the further clinical course of the patients in the next 12-month follow-up served to calculate sensitivity, specificity, as well as positive and negative predictive value of PET results.Results: In 23 patients tumor recurrence was verified by histopathology or clinical course (six local recurrences, eleven patients with distant metastases, six patients with both), 13 patients were free of tumor. In all patients with recurrent disease a true positive PET result was obtained, in eleven patients free of tumor PET was true negative, while two false positive PET results were documented. In both of these patients intraoperative findings revealed an inflammatory tumor after insufficiency of the rectal anastomosis, without evidence of carcinoma. Sensitivity for PET was 100%, specificity was 85%, positive predictive value was 92% and negative predictive value 100%.Conclusion: PET proved to be a valuable diagnostic tool in the follow-up of rectal carcinoma, with a high sensitivity and a good specificity. Indications for PET include the clinical suspicion for recurrence in combination with negative morphological imaging, and differential diagnosis of pelvic masses.     

Current and potential applications of positron emission tomography for multiple myeloma and plasma cell disorders

Fluorine-18 (18F)-fluorodeoxyglucose (FDG) positron emission tomography (PET) allows evaluation of elevated glucose metabolism in malignancies. There has been increasing interest in FDG PET/CT for plasma cell disorders since the International Myeloma Working Group outlined multiple applications of this imaging modality, including distinguishing smoldering myeloma from active multiple myeloma, confirmation of solitary plasmacytoma, and multiple indications in patients with known multiple myeloma, including determining extent of initial disease, monitoring therapy response, and detection of residual disease following therapy. The field of molecular imaging is now shifting focus from evaluation of metabolism to targeted evaluation of specific tumor markers. Targeted PET imaging targeted of CXCR4 and CD38 has advanced into translational clinical trials, bringing us closer to powerful imaging options for myeloma. In this review we discuss the current applications of FDG PET/CT in plasma cell disorders, as well as advances in targeted PET imaging.     

Untersuchung der Myokardperfusion mit der Positronen-Emissions-Tomographie

Positron emission tomography (PET) of the heart has gained widespread scientific and clinical acceptance with regard to two indications: 1) The detection of perfusion abnormalities by qualitative and semiquantitative analyses of perfusion images at rest and during physical or pharmacological stress using well-validated perfusion tracers, such as N-13 ammonia, Rb-82 rubidium chloride, or O-15 labeled water. 2) Viability imaging of myocardial regions with reduced contractility by combining perfusion measurements with substrate metabolism as assessed from F-18 deoxyglucose utilization. This overview summarizes the use of PET as a perfusion imaging method. With a sensitivity > 90% in combination with high specificity, PET is today the best-validated available nuclear imaging technique for the diagnosis of coronary artery disease (CAD). The short half-life of the perfusion tracers in combination with highly sophisticated hard- and software enables rapid PET studies with high patient throughput. The high diagnostic accuracy and the methological advantages as compared to conventional scintigraphy allows one to use PET perfusion imaging to detect subtle changes in the perfusion reserve for the detection of CAD in high risk but asymptomatic patients as well as in patients with proven CAD undergoing various treatment forms such as risk factor reduction or coronary revascularization. In patients following orthotopic heart transplantation, evolving transplant vasculopathy can be detected at an early stage. Quantitative PET imaging at rest allows for detection of myocardial viability since cellular survival is based on maintenance of a minimal perfusion and structural changes correlate to the degree of perfusion reduction. Furthermore, quantitative assessment of the myocardial perfusion reserve detects the magnitude and competence of collaterals in regions with occluded epicardial collaterals and, thus, imaging of several coronary distribution territories in one noninvasive study. The cost of PET in combination with the cost of a cyclotron facility together with the demanding methological problems have limited the availability of perfusion PET to a few sophisticated centers. Therefore, quantitative PET investigations of myocardial perfusion have been performed predominantly for scientific purposes, and the cost-effectiveness of PET in the everyday clinical setting is not yet finally proven. However, the unique possibilities of PET to study non-invasively and quantitatively myocardial perfusion and metabolism as well as cardiac innervation and pharmacokinetics of cardiac drugs have established cardiac PET as a scientific tool of the highest quality for the future.     

Imaging medullary thyroid carcinoma with persistent elevated calcitonin levels

PURPOSE: Because calcitonin level remains elevated after initial treatment in many medullary thyroid carcinoma (MTC) patients without evidence of disease in the usual imaging work-up, there is a need to define optimal imaging procedures. PATIENTS AND METHODS: Fifty-five consecutive elevated calcitonin level MTC patients were enrolled to undergo neck and abdomen ultrasonography (US); neck, chest, and abdomen spiral computed tomography (CT); liver and whole-body magnetic resonance imaging (MRI); bone scintigraphy; and 2-[fluorine-18]fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET)/CT scan (PET). RESULTS: Fifty patients underwent neck US, CT, and PET, and neck recurrence was demonstrated in 56, 42, and 32%, respectively. Lung and mediastinum lymph node metastases in the 55 patients were demonstrated in 35 and 31% by CT and in 15 and 20% by PET. Liver imaging with MRI, CT, US, and PET in 41 patients showed liver in 49, 44, 41, and 27% patients, respectively. Bone metastases in 55 patients were demonstrated in 35% by PET, 40% by bone scintigraphy, and 40% by MRI; bone scintigraphy was complementary with MRI for axial lesions but superior for the detection of peripheral lesions. Ten patients had no imaged tumor site despite elevated calcitonin level (median 196 pg/ml; range 39-816). FDG uptake in neoplastic foci was higher in progressive patients but with a considerable overlap with stable ones. CONCLUSION: The most efficient imaging work-up for depicting MTC tumor sites would consist of a neck US, chest CT, liver MRI, bone scintigraphy, and axial skeleton MRI. FDG PET scan appeared to be less sensitive and of low prognostic value.