Positron emission tomography in oncology--an introduction

Positron emission tomography has developed very much since the start in the late 1970s, especially with the development of new labelling procedures for PET-tracers. With the development of whole body imaging and the discovery that 18F-FDG allows a high sensitivity for the detection of soft tissue tumors, the clinical use has increased remarkably. The cost-effectiveness of this modality, when properly used, has been demonstrated and 18F-FDG-PET should be considered as an early alternative in patient evaluation.     

Positron emission tomography for the evaluation of pancreatic disease

Efficient techniques for native-labeling of amino acids have been combined successfully with emission tomography to yield significant improvements in pancreatic imaging. Carbon-11-labeled tryptophan appears to be the best agent available currently for imaging the pancreas. Optimum scanning times begin 30 min after tracer administration. Positron emission tomography with 11C-tryptophan is capable of defining both morphological and functional alterations in the pancreas. Tumors as small as 2 cm in diameter can be detected, but reliable differentiation of pancreatic cancer from pancreatis may not be possible even with this improved imaging technique. Longitudinal multiplane emission tomography in single-photon mode with the Pho/Con provides an efficient and satisfactory approach to pancreatic imaging with the positron-emitting radiopharmaceuticals.     

Positron emission tomography in diagnosis of occult adenocarcinoma of the breast

Occult adenocarcinoma with clinically apparent axillary lymphadenopathy represents a challenging surgical problem. Mammography is frequently unable to identify a primary breast carcinoma, and extramammary sources are common and equally difficult to identify. This may leave the clinician and patient with a conundrum of whether to proceed with "blind" mastectomy. A 35-year-old white female presented with axillary adenopathy and a normal breast physical exam. Mammography was unable to demonstrate a specific tumor. Excisional biopsy of the axillary lymph node demonstrated metastatic adenocarcinoma. Positron emission tomography showed increased uptake in the breast and the axilla, consistent with breast carcinoma and axillary metastases. The patient underwent modified radical mastectomy and pathologic review of the specimen proved infiltrating ductal carcinoma in the breast with metastatic nodes. Positron emission tomography may be helpful in localizing occult carcinoma of the breast that presents with metastatic lymph nodes and in excluding other potential primaries.     

Positron emission tomography and bone scintigraphy of an osteoclast metastasis

We present the case of a 66-year-old-male patient who suffered from a bronchial carcinoma with a rib metastasis which was detected by PET staging with a relevant 18F-FDG-Uptake. The bone scintigram with 99mTc-DPD showed a defect in this area. The aggressive disease induced no osteoblastic response.     

Positron emission tomography in partial epilepsies: the clinical point of view

Epilepsy research using positron emission tomography (PET) has advanced our understanding of the pathophysiology and neurochemical correlates of both focal and generalized epilepsies, but from the clinical viewpoint its major contribution has been in the presurgical evaluation of patients with medically intractable partial seizures. Depending on the tracer used, PET may provide information on regional cerebral blood flow and glucose metabolism, and the binding of specific ligands to receptors that are thought to be related to the genesis and propagation of epileptic activity. In this communication, we discuss the diagnostic yield, limitations and perspectives of 18F-fluorodeoxyglucose (FDG) and 11C-flumazenil (FMZ) PET in partial epilepsies. The current evidence regarding the pathophysiology of the focal changes is also presented, with an emphasis on issues which must be carefully addressed for effective and reliable clinical research.     

Positron emission tomography in primary brain tumours using cobalt-55

Primary brain tumours are usually assessed by computed tomography (CT) and magnetic resonance imaging (MRI), sometimes in conjunction with positron emission tomography (PET). We used cobalt-55 (55Co) as a calcium (Ca) tracer to visualize decaying tumour tissue, based on the fact that Ca-influx is essential in both cell death and leukocyte activation. Net 55Co uptake may be the result of cell decay, leukocyte infiltration, (re)perfusion and the pharmacological profile of 55Co. Three patients with primary malignant brain tumours (first presentation) were studied with CT, MRI and Co-PET after the intravenous administration of 0.5 mCi 55Co. Histopathological diagnosis was obtained by biopsy or resection. Co-PET demonstrated each of the brain tumours and showed good topographical agreement with CT and MRI. Co-PET provided additional detail as to the site and size of the necrotic core and the perinecrotic rim of decaying tumour. The 55Co uptake indices varied between 2.6 and 5.3. 55Co demonstrated uptake in decaying tissue, irrespective of the integrity of the blood-brain barrier. Neither necrotic nor viable tumour tissue showed affinity for 55Co. Since 55Co is readily applicable to both PET and single photon emission tomography (SPET), differences in the uptake mechanism and functional significance of the 55Co tracer are discussed in relation to 201Tl SPET. We present a (limited) pilot series of three patients to forward the claim of this new functional technique in nuclear neurology.     

Positron emission tomography of auditory sensation in deaf patients and patients with cochlear implants

The present study investigated the function of the auditory cortices in severely hearing-impaired or deaf patients and cochlear implant patients before and after auditory stimulation. Positron emission computed tomography (PET), which can detect brain activity by providing quantitative measurements of the metabolic rates of oxygen and glucose, was used. In patients with residual hearing, the activity of the auditory cortex measured by PET was almost normal. Among the totally deaf patients, the longer the duration of deafness, the lower the brain activity in the auditory cortex measured by PET. Patients who had been deaf for a long period showed remarkably reduced metabolic rates in the auditory cortices. However, following implantation of the cochlear device, the metabolic activity returned to near-normal levels. These findings suggest that activation of the speech comprehension mechanism of the higher brain system can be initiated by sound signals from the implant devices.     

Positron emission tomography and fluorodeoxyglucose studies of metabolic hyperfrontality and psychopathology in the psilocybin model of psychosis

The effects of the indolehallucinogen psilocybin, a mixed 5-HT2 and 5-HT1 agonist, on regional cerebral glucose metabolism were investigated in 10 healthy volunteers with PET and [F-18]-fluorodeoxyglucose (FDG) prior to and following a 15- or 20-mg dose of psilocybin. Psychotomimetic doses of psilocybin were found to produce a global increase in cerebral metabolic rate of glucose (CMRglu) with significant and most marked increases in the frontomedial and frontolateral cortex (24.3%), anterior cingulate (24.9%), and temporomedial cortex (25.3%). Somewhat smaller increases of CMRglu were found in the basal ganglia (18.5%), and the smallest increases were found in the sensorimotor (14.7%) and occipital cortex (14.4%). The increases of CMRglu in the prefrontal cortex, anterior cingulate, temporomedial cortex, and putamen correlated positively with psychotic symptom formation, in particular with hallucinatory ego disintegration. The present data suggest that excessive 5-HT2 receptor activation results in a hyperfrontal metablic pattern that parallels comparable metabolic findings associated with acute psychotic episodes in chronic schizophrenics and contrasts with the hypofrontality in chronic schizophrenic patients.     

Positron emission tomography in diagnosing brainstem vascular lesions that cause abnormal eye movements

PURPOSE: To evaluate the efficacy of positron emission tomography (PET) in aiding in the diagnosis of brainstem infarctions that cause abnormal eye movements. METHOD: Cerebral glucose metabolism was examined by PET with 18F-fluorodeoxyglucose as a tracer in five normal control subjects and six patients with abnormal eye movements. The PET images were registered to and superimposed on magnetic resonance images (MRIs). RESULTS: All control subjects showed little asymmetry of glucose metabolism in the brainstem, whereas all six patients demonstrated areas of low glucose metabolism in the brainstem. Areas of low metabolism seen by PET were wider than they appeared to be by MRI; MRIs even appeared normal in some patients. Asymmetry index measurements at the level of the ischemic lesion ranged between 19% and 45%. CONCLUSIONS: Positron emission tomography detected metabolic abnormality in patients with brainstem lesions that caused abnormal eye movements. Superimposing PET images on MRIs accurately localized abnormally low metabolism in the brainstem. Combined imaging with PET and MRI can be used to diagnose ischemic lesions in the brainstem from functional (PET) and morphologic (MRI) viewpoints.     

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.     

Positron emission tomography metabolic data corrected for cortical atrophy using magnetic resonance imaging

The correct interpretation of clinical positron emission tomography (PET) data depends largely on the physical limits of the PET scanner. The partial volume effect (PVE) is related to the size of the studied object compared to the spatial resolution. It represents one of the most important limiting factors in quantitative data analysis. This effect is increased in the case of atrophy, as in patients with Alzheimer disease (AD), and it influences measurement of the metabolic reduction generally seen in cerebral degeneration. In this case, interpretation can be biased, because cortical activity will be underestimated due to the atrophy. In general, anatomical images of AD patients have shown diffuse atrophy, while PET studies have found widespread hypometabolism affecting the parietal and temporal lobes. Although hypometabolic areas usually correspond to atrophic regions, they also occur without such changes. Thus, the aim is to differentiate authentic hypometabolism (decrease of glucose consumption per unit volume of gray matter) from that due to PVE from atrophy (cell loss). Consequently, we are using a method for three-dimensional (3D) correction of human PET data with 3D magnetic resonance imaging (MRI). We measured atrophy and metabolism by using both T1-weighted MR images and high and medium resolution PET scans. We injected 12 patients and controls with [18F]fluorodeoxyglucose for glucose consumption measurements. Atrophy was estimated in the following way. We isolated the cerebral structures, using a segmentation technique on the MRI scans, into gray matter (GM), white matter, and cerebrospinal fluid. We superimposed the PET images onto the MR images to obtain anatomo-functional correlations. We degraded the segmented MR images to the resolution of the PET images by a convolution process to create a PET image correction map. We corrected the metabolic PET data for the PVE. We studied the cerebral metabolic rate of glucose in the GM where metabolic variation is the most relevant to AD. By dealing with problems relating to the sensitivity to the segmentation and to the PET-MRI coregistration, computation of MRI convolution processes provided the degree of PVE on a pixel-by-pixel basis, allowing correction of hypometabolisms contained in GM PET values. Global cortical metabolism increased after correction for PVE by, on average, 29 and 24% for tomographs acquired with medium (TTV03 LETI) and high (ECAT 953B CTI/Siemens) resolution, respectively, whereas the cortical metabolism increased by 75 and 65% for the respective tomographs in AD patients. The difference of metabolism between scans after correction for PVE was less than before correction, decreasing from 31 to 17%. This difference was most marked in the frontal and temporal lobes. Fusion imaging allowed correction for PVE in metabolic data using 3D MRI and determination of whether a change in the apparent radiotracer concentration in PET data reflected an alteration in GM volume, a change in radiotracer concentration per unit volume of GM, or both.     

Evaluation of fluorodeoxyglucose positron emission tomography in the management of soft-tissue sarcomas

OBJECTIVE: This study aimed to determine whether clinical tests of ocular function and macular appearance independently can help to predict which patients with unilateral neovascular age-related macular degeneration (AMD) will have a choroidal neovascular membrane (CNVM) develop in their fellow eye. DESIGN: The study design was a prospective cohort study. PARTICIPANTS: One hundred twenty-seven patients with unilateral neovascular AMD observed for up to 4.5 years participated. INTERVENTION: Functional measurements included visual acuity, macular visual field, glare recovery time, and foveal electroretinogram amplitude and implicit time. MAIN OUTCOME MEASURE: The age-adjusted proportion of patients having a CNVM develop over follow-up assessed by the Cox proportional hazards model with stepwise selection was measured. RESULTS: On average, 8.8% of patients had a CNVM develop each year. Independent risk factors for the fellow eye were its glare recovery time in minutes (relative risk = 1.30, confidence interval = 1.10-1.54, P = 0.003) and its extent of visible macular abnormalities on a four-point scale (relative risk = 1.62, confidence interval = 1.06-2.59, P = 0.03). Of the fellow eyes that converted, the interval to have a CNVM develop was inversely related to the foveal electroretinogram implicit time. CONCLUSIONS: A slower recovery from glare and more extensive funduscopic changes appear to be independent risk factors for the development of a CNVM in the fellow eyes of patients with unilateral neovascular AMD. A slower foveal electroretinogram implicit time may be a sign of early stage CNVM development, perhaps because of outer retinal ischemia. These results have clinical management implications, particularly for those patients at high risk of having a potentially treatable form of AMD develop.     

Positron emission tomography (PET) methodology for small animals and its application in radiopharmaceutical preclinical investigation

Among the more uncommon tumors that may sometimes be encountered in the laryngeal region is the recently described giant cell tumor of the larynx. This lesion is a true neoplasm, presumably of the fibrohistiocytic series. Histologically, it closely resembles the more familiar true giant cell tumor of long bone. The laryngeal giant cell tumors appear, to date, to be nonmetastasizing lesions; it is possible that they may recur locally if incompletely excised (although this remains to be demonstrated). In view of the rarity of these tumors, a tentative diagnosis of such a neoplasm should always prompt consideration of other (more frequently encountered) differential diagnostic possibilities, including cytologically malignant giant cell-rich tumors such as malignant fibrous histiocytoma and sarcomatoid carcinoma.     

Positron emission tomography (PET) and (F-18)-fluorodeoxyglucose in (FDG) in cancerology

Positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) is a scintigraphic imaging technique undergoing a rapid growth in the field of oncology. The constant progress of the detectors, either CDET or PET dedicated cameras, allows to obtain in routine conditions images with a 5 mm spatial resolution. Absolute tracer uptake quantification is also possible, which allows to evaluate objectively therapy efficacy. The mechanisms of FDG tissular accumulation are now better understood. Increase of glycolysis and of transmembrane transport of glucose seems to be at the origin of the high tumorous accumulation of FDG. The main current oncologic application of FDG PET is the diagnosis of malignancy of the isolated pulmonary nodules, with a sensitivity of more than 95%, and in the staging of lung cancer where PET shows higher performances than conventional imaging. The same stands in cutaneous melanoma and for malignancies of the digestive tract, either in colorectal, pancreatic or esophageal localizations. In colorectal cancers, the role of PET has for long being recognized in the differential diagnosis between recurrence and postoperative fibrosis. In the head and neck tumors, FDG also allows to differentiate between recurrence and postradiation necrosis. In lymphoma, the most suitable site for biopsy can be identified on a PET scan and therapy efficacy can also be assessed. In breast cancer, the detection of metastases seems to be possible with FDG. In brain and thyroid cancers, the role of FDG PET remains to be further determined. The low uptake of FDG in prostate cancer metastasis is not in favor of its use in this indication. In conclusion, the indications of FDG PET in oncology are now becoming more precise and it can be expected that clinical PET centers will soon appear in France.     

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.     

Positron emission tomography with 18F-FDG to detect residual disease after therapy for malignant lymphoma

We retrospectively evaluated the use of 18F-FDG PET for assessment of residual disease in 27 patients after therapy for malignant lymphoma. The images were evaluated qualitatively and quantitatively using standardized uptake values (SUV). All findings were validated either by biopsy or by clinical follow-up and compared with corresponding CT findings. The impact of blood glucose concentration, body weight, body surface area, lesion diameter and the time between injection and imaging on the SUVs were analysed. All 15 patients with biopsy-proven residual disease or relapse during follow-up and 11 of 12 patients who remained relapse-free were correctly identified by qualitative interpretation of the PET images. A case of pneumonitis after radiotherapy/chemotherapy accounted for the only false-positive finding. Compared with CT imaging, PET had a significantly higher specificity (P < 0.01), accuracy (P < 0.05) and positive predictive value (P < 0.05). The mean and maximum SUV of the tumour lesions were positively correlated to lesion diameter (P < 0.01) and imaging time post-injection (P < 0.01). Standardized uptake values corrected for the partial volume effect and normalized to a standardized imaging time (SUVBPT) were significantly higher (P < 0.05) in high-grade than in low-grade non-Hodgkin's lymphoma. In conclusion, 18F-FDG PET may help in the identification of patients who need additional treatment after the completion of conventional therapy. Qualitative image interpretation appears sufficient for this purpose.     

Prognostic factors in metastatic melanoma

BACKGROUND: Each year, 6000 people die in the United States from metastatic melanoma. Further study of factors affecting the prognosis of patients with this disease is needed. METHODS: The authors analyzed response and survival data from 635 patients who had entered three Eastern Cooperative Oncology Group trials for metastatic melanoma. RESULTS: Factors associated with poorer survival after study entry included poor performance status and the presence of symptoms, such as reduced appetite, fever, or nausea/vomiting. Male patients had poor survival, as did patients entering the study less than 1 year after a documented recurrence to study entry. As expected, characteristics of the initial primary disease (treatment and symptoms) had little association with survival after entering the advanced disease protocol. Two summary measures of the extent of metastatic involvement had a strong influence on survival. These were the number of nonbone metastases and the clinician's assessment as to the most significant metastatic site. Patients with the liver as their clinically most significant metastatic site had a poorer prognosis than those otherwise classified, including those with central nervous system metastases. The prognosis also worsened with an increasing number of sites of nonbone metastases, including skin and soft tissue. Tumor response occurred in only 11% of the patients. Patients with poor performance status and those with lung involvement had a significantly lower response rate than did others. Although the frequency of response was low, patients with objective responses survived significantly longer than did the nonresponders (based on an analysis appropriately adjusted for the time of response using a time-dependent proportional-hazards model). CONCLUSIONS: These results provide useful guidelines for the design and analysis of clinical trials in metastatic melanoma.