Current role of positron emission tomography in thoracic oncology

Continuing advances in PET imaging have resulted in an improved ability to evaluate thoracic malignancies. Published reports demonstrate that PET provides accurate, non-invasive detection and staging of thoracic malignancy. Preliminary studies suggest that PET may also be able to assess the therapeutic response accurately. The studies investigating PET have been relatively small but have shown statistically significant advantages over conventional non-invasive techniques in accuracy and possibly even cost/benefit performance in thoracic malignancies.     

Detection of recurrent and metastatic colorectal cancer: comparison of positron emission tomography and computed tomography

BACKGROUND: This study evaluates the clinical value of positron emission tomography (PET) with 2-[F-18] fluoro-2-deoxy-D-glucose (FDG) as compared to computed tomography (CT) in patients with suspected recurrent or metastatic colorectal cancer (CRC). METHODS: A retrospective review of the records of 58 patients who had FDG-PET for evaluation of recurrent or advanced primary CRC was performed. FDG-PET results were compared with those of CT and correlated with operative and histopathologic findings, or with clinical course and autopsy reports. RESULTS: Recurrent or advanced primary CRC was diagnosed in 40 and 11 patients, respectively. The sensitivity and specificity of FDG-PET were 91% and 100% for detecting local pelvic recurrence, and 95% and 100% for hepatic metastases. These values were superior to CT, which had sensitivity and specificity of 52% and 80% for detecting pelvic recurrence, and 74% and 85% for hepatic metastases. FDG-PET correctly identified pelvic recurrence in 19 of 21 patients; CT was negative in 6 of these patients and equivocal in 4. FDG-PET was superior to CT in detecting multiple hepatic lesions and influenced clinical management in 10 of 23 (43%) patients. CONCLUSION: FDG-PET is more sensitive than CT in the clinical assessment of patients with recurrent or metastatic CRC, and provides an accurate means of selecting appropriate treatment for these patients.     

Attenuation-corrected 99mTc-tetrofosmin single-photon emission computed tomography in the detection of viable myocardium: comparison with positron emission tomography using 18F-fluorodeoxyglucose

OBJECTIVES: The purpose of this study was to assess the efficacy of attenuation-corrected (AC) technetium-99m (99mTc)-tetrofosmin single-photon emission computed tomography (SPECT) in detecting viable myocardium compared to 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET). BACKGROUND: The role of 99mTc-labeled perfusion tracers in the assessment of myocardial viability remains controversial. Attenuation artifacts affect the diagnostic accuracy of SPECT images. METHODS: Twenty-four patients with coronary artery disease (mean left ventricular ejection fraction 30%) underwent resting 99mTc-tetrofosmin SPECT and FDG PET imaging. Both AC and non-attenuation-corrected (NC) SPECT images were generated. RESULTS: Using a 50% threshold for viability by FDG PET, the percentage of concordant segments of viability between 99mTc-tetrofosmin and FDG on the patient basis increased from 79.8%+/-14.0% (mean+/-SD) on the NC images to 90.8%+/-10.6% on the AC images (p=0.002). The percentage of 99mTc-tetrofosmin defect segments within PET-viable segments, an estimate for the degree of underestimation of viability, decreased from 19.8%+/-15.2% on the NC images to 9.7%+/-12.6% on the AC images (p=0.01). Similar results were obtained when a 60% threshold was used to define viability by FDG PET. When the anterior-lateral and inferior-septal regions were separately analyzed, the effect of attenuation correction was significant only in the inferior-septal region. CONCLUSIONS: The results indicate that AC 99mTc-tetrofosmin SPECT improves the detection of viable myocardium mainly by decreasing the underestimation of viability particularly in the inferior-septal region, although some underestimation/overestimation of viability may still occur even with attenuation correction.     

Clinical positron emission tomography for brain tumors: comparison of fludeoxyglucose F 18 and L-methyl-11C-methionine

PURPOSE: To evaluate the differences between fludeoxyglucose F 18 (FDG) and L-methyl-11C-methionine (11C-methionine) as tracers for positron emission tomography (PET) in the evaluation of brain tumors. METHODS: We analyzed 10 patients with histologically verified cerebral glioma or meningioma and 1 patient with a neuroradiologic diagnosis of low-grade glioma by using FDG, 11C-methionine, and PET. We qualitatively and quantitatively evaluated the extent and degree of accumulation of FDG and 11C-methionine in the tumor tissue. RESULTS: Although PET with FDG depicted malignant tumors as a hot spot in all cases, it was not able to delineate the extent of the tumor. Conversely, PET with 11C-methionine outlined the tumors as areas of increased accumulation of 11C-methionine, regardless of the degree of malignancy. CONCLUSION: PET with FDG and with 11C-methionine can play complementary roles in the evaluation of brain tumors.     

Evaluation of pancreatic tumors with positron emission tomography and F-18 fluorodeoxyglucose: comparison with CT and US

PURPOSE: To assess the clinical value of positron emission tomography (PET) with fluorine-18-labeled fluorodeoxyglucose (FDG) for identification of pancreatic carcinoma. MATERIALS AND METHODS: Forty-six patients suspected of having a pancreatic neoplasm and who were to undergo surgery prospectively underwent FDG PET, computed tomography (CT), and transabdominal ultrasound (US). Endoscopic US was performed in 40 patients. Images were independently interpreted and compared with the histopathologic findings at surgery (41 patients) or with clinical follow-up findings (five patients). RESULTS: In 33 of 35 patients, foci of pancreatic carcinomas (10-100 mm in diameter) were identified as an increase in FDG uptake, whereas CT, transabdominal US, and endoscopic US depicted the foci in 31, 31, and 28, cases, respectively. Among 11 benign lesions, nine showed no increased FDG uptake (specificity = 82%). Specificities of the other modalities were lower. False-positive findings were obtained in a case of chronic active pancreatitis and in a serous cystadenoma. CONCLUSION: FDG PET, which provides "biochemical" information, is accurate in identifying pancreatic carcinoma and may be a method of choice when imaging equivocal masses detected with other "anatomic" imaging studies.     

Cerebral blood flow and personality: a positron emission tomography study

OBJECTIVE: To determine current practice patterns of obtaining informed consent for infertility treatment by reproductive endocrinologists and to assess changes in response to reports of an association between ovulation induction and ovarian cancer. METHODS: Board-certified reproductive endocrinologists (n = 575) were surveyed by mail regarding how they informed patients and obtained consent for infertility treatments and how their practices had been influenced by studies suggesting a link between ovulation induction and ovarian cancer. Data were analyzed using chi2 and logistic regression analyses. RESULTS: The return rate was 62.1% (357 of 575 surveys). Most respondents (92%) used discussions with physicians to inform their patients of risks and benefits of all infertility treatments. Additional means, such as audiovisual aids, were used significantly more often for assisted reproductive technologies (including intracytoplasmic sperm injection and use of donated eggs) than for less invasive therapies (31-43% versus 4-11%, P < .001). Most physicians (46-66%) used verbal consent alone for hysterosalpingogram, intrauterine insemination, and ovulation induction. Formal written consent was used significantly more often for the various assisted reproductive technologies than for hysterosalpingogram, intrauterine insemination, or ovulation induction (94-95% versus 26-44%). Although most physicians (70%) did not believe that ovulation induction increases the risk of ovarian cancer, 83% addressed this risk when obtaining consent and 47% reported changing their practices since an association was reported. Common changes included limiting length of treatment and addressing ovarian cancer risk. CONCLUSION: Current practice patterns of obtaining informed consent for various infertility treatments by board-certified reproductive endocrinologists show, as expected, that informed consent is more rigorous for assisted reproductive technologies. Although most surveyed did not believe that ovulation induction increases risk of ovarian cancer, the majority of physicians addressed that risk when obtaining consent and nearly half changed their practices on the basis of a possible association.     

Short-term and long-term verbal memory: a positron emission tomography study

Short-term and long-term retention of experimentally presented words were compared in a sample of 33 healthy normal volunteers by the [15O]H2O method with positron emission tomography (PET). The design included three conditions. For the long-term condition, subjects thoroughly studied 18 words 1 week before the PET study. For the short-term condition, subjects were shown another set of 18 words 60 sec before imaging, with instructions to remember them. For the baseline condition, subtracted from the two memory conditions, subjects read a third set of words that they had not previously seen in the experiment. Similar regions were activated in both short-term and long-term conditions: large right frontal areas, biparietal areas, and the left cerebellum. In addition, the short-term condition also activated a relatively large region in the left prefrontal region. These complex distributed circuits appear to represent the neural substrates for aspects of memory such as encoding, retrieval, and storage. They indicate that circuitry involved in episodic memory has much larger cortical and cerebellar components than has been emphasized in earlier lesion studies.     

Computed tomography and positron emission tomography in the pre-operative staging of oesophageal carcinoma

Because patients with carcinoma of the oesophagus usually present with advanced disease and surgery has a high mortality with cure in less than 10% of patients, pre-operative staging to select appropriate patients is necessary. Computed tomography (CT) plays an important role in staging but has well recognized limitations. Positron emission tomography (PET) which provides physiological information may therefore be a better alternative. OBJECTIVE: To compare the findings of CT and positron emission tomography (PET) with 2-[18fluorine]-fluoro-2-deoxy-D-glucose (FDG) in the pre-operative staging of oesophageal carcinoma. MATERIALS AND METHODS: Twenty-five patients with biopsy proven oesophageal cancer had pre-operative staging using CT and FDG-PET. The studies were read independently and full histological confirmation was obtained in 19 patients. Four parameters were studied: the primary tumour, peri-oesophageal lymph nodes, liver metastases and left gastric lymph nodes. RESULTS: PET visualized all primary tumours; CT missed one. CT identified 4/8 patients with involved peri-oesophageal nodes and PET 3/8. CT identified 5/9 patients with left gastric adenopathy and PET 1/9. PET visualized a liver metastasis missed on CT and appeared to be better in assessing residual tumour. PET did identify distant metastases not seen on CT in seven patients. CONCLUSIONS: The two techniques are both effective in showing the primary tumour and about equally sensitive in the demonstration of peri-oesophageal nodes. PET is probably more sensitive than CT for the detection of distant metastases.     

Possible uses of positron emission tomography in breast carcinoma

The aetiology, biochemistry, clinical features and complications of histologically confirmed hepatic cirrhosis in 45 patients (26 females, 19 males) seen at the University Hospital of the West Indies, Jamaica, between 1984 and 1994 are presented. The age range was 1 to 72 years (mean 48 years). Abdominal swelling and weight loss were the commonest symptoms, occurring in 51% and 47% of patients, respectively. Jaundice was a presenting feature in 44%. Hepatomegaly was present in 71% of patients and splenomegaly in 33%. The aetiological factors were: alcohol (36%), bush tea (18%), chronic active hepatitis (11%), drugs (7%), and haemochromatosis (2%). Hepatitis B surface antigen was detected in 2 of 20 patients tested. 24% of the patients also had diabetes mellitus., 29% were anaemic, 29% were thrombocytopenic, 4% were leukopenic, and the prothrombin time was prolonged in 22%. The albumin/globulin ratio was reversed in 71% of the patients. The alkaline phosphatase was elevated in 56%, the aspartate aminotransferase was increased in 58% and the gamma glutamyl transpeptidase in 56%. 56% of the patients had macronodular cirrhosis; the liver showed a micronodular pattern in 18%; 7% had biliary cirrhosis; 7% chronic active hepatitis with cirrhosis; and 13% showed a mixed macro-micronodular pattern. Ascites and fluid overload developed in 44% of the patients. Hepatic encephalopathy occurred in 18% and upper gastrointestinal bleeding in 18%.     

The role of positron emission tomography in pharmacokinetic analysis

The physiological and biochemical measurements that can be performed noninvasively in humans with modern imaging techniques offer great promise for defining the precise state of a patient's disease and its response to therapy. In general, there are two critical points in drug development when PET measurements are likely to be particularly useful: (1) In preclinical studies, a new drug can be precisely compared to standard therapies or a series of analogs can be screened for further development on the basis of performance in appropriate animal models. (2) In phase I-II human studies, classic pharmacokinetic measurements can be coupled with imaging measurements (a) to define optimal dosing schedule; (b) to define the potential utility of interventions in particular clinical situations; and (c) to formulate the design of phase III studies that are crucial for drug licensure. In general, the types of measurements that are possible can be grouped into the following categories: 1. In those situations in which the drug can be radiolabeled, the time course of tissue delivery can be determined noninvasively in vivo in health and disease. Such information should be useful for determining dosing schedules, establishing efficacy, and predicting possible toxicity. 2. Ligand-receptor binding can be assessed in vivo in two ways. The ability of the drug to displace standard radiolabeled ligands from their receptors can be determined; alternatively, labeled drug can be used to more directly assess the distribution and time course of binding. These measurements are particularly useful for studying drugs that are active in the central nervous and cardiovascular systems. 3. Measurements of tissue metabolism will be useful in determining the effects of therapies aimed at particular metabolic abnormalities. In addition, these measurements may be useful in defining viability and function of tissues in such widely disparate clinical situations as cancer chemotherapy and cardiology. For example, effects of CNS or cardiovascular drugs can be monitored by observing 18FDG metabolism in brain and heart. We suggest that the joining of classic clinical pharmacology to exquisite imaging measurements will help form the basis for 21st-century clinical drug development.     

Clinical use of positron emission tomography in cerebrovascular diseases

In this article the author reviews the state-of-the-art regarding the clinical applications of positron emission tomography (PET) in cerebrovascular diseases. First, the basic methodology and physiology of cerebral blood flow and metabolism as it pertains to cerebrovascular disease are summarized. The reader is then given an account of the main findings from this technique with respect to (1) the assessment of the hemodynamic and metabolic effects of carotid artery disease in the perspective of surgical versus medical management, (2) the changes in brain perfusion and metabolism in acute ischemic stroke as they relate to the issue of patient management, outcome predictability, and screening in therapeutic trials, and (3) mapping of the remote metabolic effects of stroke and their clinical relevance.     

Pre-processing variance reducing techniques in multispectral positron emission tomography

Stochastic fluctuations and systematic errors severely restrict the potential of multispectral acquisition to improve scatter correction by energy-dependent processing in high-resolution positron emission tomography (PET). To overcome this limitation, three pre-processing approaches which reduce stochastic fluctuations and systematic errors without degrading spatial resolution were investigated: statistical variance was reduced by smoothing acquired data in energy space, systematic errors due to nonuniform detector efficiency were minimized by normalizing the data in the spatial domain and the overall variance was further reduced by selecting an optimal pre-processing sequence. Selection of the best protocol to reduce stochastic fluctuations entailed comparisons between four smoothing algorithms (prior constrained (PC) smoothing, weighted smoothing (WS), ideal low-pass filtering (ILF) and mean median (MM) smoothing) and permutations of three pre-processing procedures (smoothing, normalization and subtraction of random events). Results demonstrated that spectral smoothing by WS, ILF and MM efficiently reduces the statistical variance in both the energy and spatial domains without observable spatial resolution loss. The ILF algorithm was found to be the most convenient in terms of simplicity and efficiency. Regardless of the position of subtraction of randoms in the sequence, reduction of the systematic errors by normalization followed by spectral smoothing to suppress statistical noise produced the best results. However, subtraction of random events first in the sequence reduces computation load by half since the need to pre-process this distribution before subtraction is removed. In summary, normalizing data in the spatial domain and smoothing data in energy space are essential steps required to reduce systematic errors and statistical variance independently without degrading spatial resolution of multispectral PET data.     

Imaging of the dopaminergic neurotransmission system using single-photon emission tomography and positron emission tomography in patients with parkinsonism

Parkinsonism is a feature of a number of neurodegenerative diseases, including Parkinson's disease, multiple system atrophy and progressive supranuclear palsy. The results of post-mortem studies point to dysfunction of the dopaminergic neurotransmitter system in patients with parkinsonism. Nowadays, by using single-photon emission tomography (SPET) and positron emission tomography (PET) it is possible to visualise both the nigrostriatal dopaminergic neurons and the striatal dopamine D2 receptors in vivo. Consequently, SPET and PET imaging of elements of the dopaminergic system can play an important role in the diagnosis of several parkinsonian syndromes. This review concentrates on findings of SPET and PET studies of the dopaminergic neurotransmitter system in various parkinsonian syndromes.     

Whole-body 2-[18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) for accurate staging of Hodgkin's disease

BACKGROUND: Staging of Hodgkin's disease (HD) is accomplished by a variety of invasive and non-invasive modalities. This prospective study was undertaken to investigate the value of whole-body positron emission tomography (PET) with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) in defining regions involved by lymphoma compared with conventional staging methods in patients with HD. PATIENTS AND METHODS: Fourty-four newly diagnosed patients with HD underwent FDG-PET as part of their initial staging work-up. PET findings were correlated with findings of conventional staging including computed tomography, ultrasound, bone scanning, bone marrow biopsy, liver biopsy and laparotomy. When results of FDG-PET differed to those obtained by conventional methods reevaluation was performed by biopsy, if possible, or magnetic resonance imaging. RESULTS: The results of FDG-PET were compared with three hundred twenty-one conventional staging procedures performed in 44 patients. FDG-PET was positive in 38 of 44 (86%) patients at sites of documented disease. PET detected additional lesions in five cases previously not identified by conventional staging methods. In another case a nodal lesion suspect on CT was negative at FDG-PET and was settled as true negative by biopsy. As a consequence of PET findings five patients had to be upstaged and one patient had to be downstaged, resulting in changes in treatment strategy in all six cases (14%). FDG-PET failed to visualize sites of HD in four patients. In two of our patients a false positive PET result was obtained. CONCLUSIONS: Our data indicate that FDG-PET provides an imaging technique that appears to visualize involved lesions in most patients with HD and is useful in the management of these patients.     

The advantage of using positron emission tomography in drug research

A large problem in drug discovery is to find relevant in vitro or in vivo animal models and to be able to extrapolate the results obtained to humans. Drug research now benefits from the fast development of imaging technologies that trace radiolabelled molecules directly in the human brain. Positron emission tomography (PET) and allied techniques use molecules that are labelled with short-lived radioisotopes and injected intravenously. The most straightforward approach is to radiolabel a new potential drug and then to trace its anatomical distribution and binding in the brain. An indirect approach is to study how the unlabelled drug inhibits specific radioligand binding. The demonstration of quantitative relationships between drug binding in vivo and drug effects in patients is used to validate targets for drug action and to optimize clinical treatment.     

Magnetic resonance imaging and positron emission tomography of band heterotopia

A case of band heterotopia was reported with findings of positron emission tomography (PET). The patient was an 8-year-old girl who had mild mental retardation and intractable partial epilepsy. Her MRI showed another diffuse layer of gray matter underlying the normal-looking cortex and separated from it by an apparently normal layer of white matter. PET scan with [18F]fluorodeoxyglucose revealed that band heterotopia had the same degree of glucose metabolism as that of the overlying cortex.     

Imaging of myocardial perfusion and metabolism with positron emission tomography

Positron emission tomography (PET) has been providing new information in the diagnosis and the pathophysiological assessment of heart diseases. The PET tracers commonly used in Japan are 13N-ammonia, 18F-fluorodeoxyglucose (FDG) for imaging of myocardial perfusion and metabolism, respectively. Measurement of regional myocardial blood flow by 13N-ammonia dynamic PET scan and a compartment model analysis is applied to the functional estimation of coronary stenotic lesions and the detection of perfusion abnormalities in hypertrophic heart diseases, familial hyperchlesterolemia and other diseases with possible microvascular lesions. 18F-FDG is commonly used to differentiate ischemic but viable tissue from myocardial scar in coronary artery disease and also used to detect cardiac tumor and the cardiac involvement in sarcoidosis. In addition to these two tracers, 11C-acetate is now expected to provide the clinical analysis of pathophysiology of heart failure by estimating the efficiency of energy conversion of the heart into external work.     

A review of functional neuroimaging in mood disorders: positron emission tomography and depression

OBJECTIVE: To examine the progress of positron emission tomography (PET) as a tool for understanding the psychobiology of mood disorders, particularly major depression and bipolar disorder. METHOD: Review of the literature on functional imaging of mood disorders. RESULTS: Functional imaging techniques have been used in psychiatric research as a noninvasive method to study the behaviour and function of the brain. Techniques used so far have involved the manipulation of emotion in healthy volunteers, the evaluation of depressed (unipolar and bipolar as well as secondary depression), manic, and normal subjects under resting and various activation conditions, such as cognitive activation, acute pharmacological challenge, and chronic thymoleptic treatments. As a result, functional imaging studies tend to support abnormalities in specific frontal and limbic regions. CONCLUSION: Different PET methods demonstrate consistent abnormalities in the prefrontal, cingulate, and amygdala regions. These findings are in agreement with past animal and clinical anatomical correlates of mood and emotions.