Salvatore U. Berlangieri

Imaging of amyloid β in Alzheimer's disease with 18F-BAY94-9172, a novel PET tracer: proof of mechanism

BACKGROUND Amyloid-beta (Abeta) plaque formation is a hallmark of Alzheimers disease (AD) and precedes the onset of dementia. Abeta imaging should allow earlier diagnosis, but clinical application is hindered by the short decay half-life of current Abeta-specific ligands. (18)F-BAY94-9172 is an Abeta ligand that, due to the half-life of (18)F, is suitable for clinical use. We thus studied the effectiveness of this ligand in identifying patients with AD. METHODS 15 patients with mild AD, 15 healthy elderly controls, and five individuals with frontotemporal lobar degeneration (FTLD) were studied. (18)F-BAY94-9172 binding was quantified by use of the standardised uptake value ratio (SUVR), which was calculated for the neocortex by use of the cerebellum as reference region. SUVR images were visually rated as normal or AD. FINDINGS (18)F-BAY94-9172 binding matched the reported post-mortem distribution of Abeta plaques. All AD patients showed widespread neocortical binding, which was greater in the precuneus/posterior cingulate and frontal cortex than in the lateral temporal and parietal cortex. There was relative sparing of sensorimotor, occipital, and medial temporal cortex. Healthy controls and FTLD patients showed only white-matter binding, although three controls and one FTLD patient had mild uptake in frontal and precuneus cortex. At 90-120 min after injection, higher neocortical SUVR was observed in AD patients (2.0 [SD 0.3]) than in healthy controls (1.3 [SD 0.2]; p<0.0001) or FTLD patients (1.2 [SD 0.2]; p=0.009). Visual interpretation was 100% sensitive and 90% specific for detection of AD. INTERPRETATION (18)F-BAY94-9172 PET discriminates between AD and FTLD or healthy controls and might facilitate integration of Abeta imaging into clinical practice.

Visual Assessment Versus Quantitative Assessment of 11C-PIB PET and 18F-FDG PET for Detection of Alzheimer's Disease

Amyloid-β (Aβ) imaging with N-methyl-11C-2-(4′-methylamino-phenyl)-6-hydroxy-benzothiazole (11C-6-OH-BTA-1; also known as 11C-PIB) shows a robust increase in cortical binding in Alzheimers disease (AD). The aim of this study was to explore the clinical potential of Aβ imaging for the diagnosis of AD by comparison of the accuracy of visual reading of 11C-PIB images with quantitative analysis and 18F-FDG. Methods: Fifteen AD patients (age, 71.1 ± 11.3 y [mean ± SD]; mini-mental state examination [MMSE], 18.9 ± 9.3 [mean ± SD]) and 25 healthy control (HC) subjects (age, 71.9 ± 6.82 y; MMSE ≥ 28) underwent 90-min dynamic 11C-PIB PET and 20-min static 18F-FDG PET. 11C-PIB images, generated from data acquired between 40 and 70 min after injection, and 18F-FDG images were rated separately by 2 readers as normal, possible AD, or probable AD. Quantitative analyses used the distribution volume ratio (DVR) of frontal cortex, parietotemporal cortex, posterior cingulate, and caudate nucleus for 11C-PIB and standardized uptake value ratio (SUVR) of parietotemporal cortex and posterior cingulate for 18F-FDG, using cerebellar cortex as the reference region. Receiver-operating-characteristic (ROC) analysis was performed to compare the accuracy of quantitative measures. To determine the effect of age on diagnostic accuracy, the median age of the AD subjects (74 y) was chosen to separate the cohort into younger (64.4 ± 5.8 y) and older (78.6 ± 4.1 y) groups. Results: Visual agreement between readers was excellent for 11C-PIB (κ = 0.90) and good for 18F-FDG (κ = 0.56). 11C-PIB was more accurate than 18F-FDG both on visual reading (accuracy, 90% vs. 70%, P = 0.05) and ROC analysis (95% vs. 83%, P = 0.02). Accuracy declined more with 18F-FDG than with 11C-PIB in the older group. Conclusion: Visual analysis of 11C-PIB images appears more accurate than visual reading of 18F-FDG for identification of AD and has accuracy similar to quantitative analysis of a 90-min dynamic scan. The accuracy of 11C-PIB PET is limited by cortical binding in some healthy elderly subjects, consistent with postmortem studies of cerebral Aβ. Longitudinal follow-up is required to determine if this represents detection of preclinical AD.

The contribution of 18F-fluoro-2-deoxy-glucose positron emission tomographic imaging to radiotherapy planning in lung cancer

A retrospective analysis was performed to determine whether coronal thoracic [18F]fluoro-2-deoxy-glucose positron emission tomography (FDG-PET) scans, if viewed at the time of radiotherapy (RT) planning, would have influenced the anterior-posterior (AP) RT volumes that were administered to a group of unoperated lung cancer patients. Viewing of PET and diagnostic images enabled a qualitative assessment of whether abnormal thoracic PET activity was present in areas regarded as normal by diagnostic imaging; this would, therefore, have influenced the RT volume if done prospectively. Additionally a method of graphical co-registration was devised to quantitate the adequacy of coverage of each patients abnormal PET activity by his/her actual RT field. Of 15 patients analyzed, 26.7% (four patients) would have had their RT volume influenced by PET findings, highlighting the potential value of PET in treatment planning.

CLINICAL ROLE OF F-18 FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY FOR DETECTION AND MANAGEMENT OF RENAL CELL CARCINOMA

PURPOSE We evaluate the accuracy of F-18 fluorodeoxyglucose (FDG)-positron emission tomography (PET) for staging and management of renal cell carcinoma. MATERIALS AND METHODS FDG-PET was performed in 25 patients with known or suspected primary renal tumors and/or metastatic disease and compared with conventional imaging techniques, including computerized tomography (CT). Histopathological confirmation was obtained in 18 patients and confirmation of the disease was by followup in the remainder. The impact of FDG-PET on disease management was also assessed. RESULTS Of the 17 patients with known or suspected primary tumors FDG-PET was true positive in 15, true negative in 1 and false-negative in 1. Comparative CT was true positive in 16 patients and false-positive in 1. The accuracy of FDG-PET and CT was similar (94%). All patients would have undergone radical nephrectomy after conventional imaging findings but FDG-PET results altered treatment decisions for 6 (35%), of whom 3 underwent partial nephrectomy and 3 avoided surgery due to confirmation of benign pathology or detection of unsuspected metastatic disease. Of the 8 cases referred for evaluation of local recurrence and/or metastatic disease FDG-PET changed treatment decisions in 4 (50%), with disease up staged in 3 and recurrence excluded in 1. Compared with CT, FDG-PET was able to detect local recurrence and distant metastases more accurately and differentiated recurrence from radiation necrosis. CONCLUSIONS FDG-PET accurately detected local disease spread and metastatic disease in patients with renal cell carcinoma and altered treatment in 40%. FDG-PET may have a role in the diagnostic evaluation of patients with renal cell carcinoma preoperatively and staging of metastatic disease.

Autosomal dominant nocturnal frontal lobe epilepsy: Demonstration of focal frontal onset and intrafamilial variation

Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a newly recognized autosomal dominant partial epilepsy. We studied seizure localization and intrafamilial variation using video-EEG monitoring (VEM) and functional neuroimaging in two pairs of subjects from unrelated families. The clinical features of seizures were similar from seizure to seizure in each individual, but varied between individuals. As is often found in frontal lobe epilepsies, ictal EEG localization was imprecise in three of four cases. One patient showed a consistent left fronto-polar onset that was corroborated by congruent focal hypometabolism on interictal PET and focal hyperperfusion on ictal single photon emission computed tomography (SPECT). A second case studied with ictal SPECT showed a right parasagittal, midfrontal focus. We conclude that this autosomal dominant epilepsy syndrome, which in one of the two families was due to a known neuronal nicotinic acetylcholine receptor mutation, causes frontal lobe foci that are unilateral and in variable locations in different individuals.

Hippocampal Atrophy Is Not a Major Determinant of Regional Hypometabolism in Temporal Lobe Epilepsy

Summary: Purpose: The pathophysiologic basis for the [18F]fluorodeoxyglucose positron‐emission tomography (FDG‐PET) temporal lobe hypometabolism in patients with hippocampal sclerosis (HS) is uncertain. We tested the hypothesis that hippocampal atrophy, which is strongly correlated with hippocampal cell loss, is largely responsible for the regional hypometabolism in HS.

Positron emission tomography and epilepsy.

PURPOSE This review examines the current role of positron emission tomography (PET) in the investigation and management of patients with epilepsy. PROCEDURES A literature review utilizing MEDLINE(R) and other sources was undertaken. For the comparison of the accuracy of PET with magnetic resonance imaging (MRI) for seizure focus localization, only publications since 1994 were examined. Individual patient data was tabulated to provide figures for seizure focus localization rates for different types of focal epilepsy and the prognostic value of PET findings for epilepsy surgery outcome. RESULTS The majority of PET studies used 2-deoxy-2-[18F]fluoro-D-glucose (FDG). The epileptogenic sites typically show reduced FDG uptake (hypometabolism). In patients with intractable temporal lobe epilepsy (TLE), unilateral temporal lobe hypometabolism (UTH) corresponding to the seizure focus was seen in 86% of patients. In the same population, MRI demonstrated relevant abnormalities in 76%. UTH contralateral to the seizure focus was rarely seen (3%). Following temporal lobectomy, 86% of patients with ipsilateral UTH had a good outcome. When MRI was normal, UTH predicted a good outcome in 82%. Fifty percent with bitemporal hypometabolism had independent bilateral foci, and in those who proceeded to surgery only 50% had a good result. In extratemporal epilepsy, hypometabolism relevant to the focus was seen in 67% but, as in TLE, it was often more extensive than pathological abnormality. Recently evidence of a role for 11C-Flumazenil has emerged with reduced binding in the primary epileptogenic site. 11C-Flumazenil abnormalities appear more restricted to abnormal cortex and may be a better guide to the extent of resection required for surgical success. CONCLUSIONS FDG-PET has a key role in the evaluation of patients with intractable partial epilepsy, particularly when surgery is a treatment option. Development and application of more specific biochemical probes may further improve the clinical value of PET for the understanding and treatment of epilepsy.

Impact of 2-Deoxy-2[F-18]Fluoro-d-Glucose Positron Emission Tomography on the Management of Patients with Advanced Melanoma

Accurate staging of patients with melanoma is vital to guide appropriate treatment. 2-Deoxy-2-[F-18]fluoro-d-glucose (FDG)-positron emission tomography (PET) has been reported to be a sensitive and specific technique for the staging of advanced melanoma, however, few studies provide information regarding its impact on patient management. We retrospectively reviewed the FDG-PET scan results of 92 patients with melanoma who had 126 scans performed over a six-year period. These patients were seen at the specialist melanoma clinic at our Institution, and 84 patients (92%) had stage III or IV disease. FDG-PET scan results were correlated with computed tomography (CT) scans and other imaging when available, and with clinical follow-up of a minimum of three to six months. The impact of FDG-PET scans on patient management was also assessed. On a lesion-by-lesion analysis, FDG-PET had a sensitivity of 92%, a specificity of 88%, and an accuracy of 91%. FDG-PET correctly affected the clinical decision-making process in 40 of 126 patient studies (32%), particularly assisting in the selection of patients for surgery. FDG-PET has an important role in guiding the management of patients with advanced melanoma, particularly when surgery is contemplated.

Comparison of dobutamine echocardiography and positron emission tomography in patients with chronic ischemic left ventricular dysfunction

OBJECTIVES The aim of this study was to correlate dobutamine-induced contractile reserve as detected by echocardiography with findings on positron emission tomography in patients with chronic ischemic left ventricular dysfunction. BACKGROUND Contractile reserve induced by low dose dobutamine infusion has been proposed as a marker of myocardial viability. METHODS Sixty patients with stable coronary artery disease and left ventricular dysfunction (mean ejection fraction [+/- SD] 29 +/- 10%) underwent transthoracic echocardiography with dobutamine infusion (up to 10 micrograms/kg body weight per min) and positron emission tomography with nitrogen-13 ammonia and fluorine-18 (F-18) fluorodeoxyglucose as a perfusion and a metabolic tracer, respectively. Regional wall motion, perfusion and metabolism were analyzed semiquantitatively by using a 16-segment model. Segments with F-18 fluorodeoxyglucose uptake > 50% were considered viable on positron emission tomography. RESULTS After dobutamine infusion, hemodynamic variables changed significantly, and myocardial ischemia was evident in 17 patients. All 60 patients had dysfunctional myocardium considered viable on positron emission tomography (8 +/- 4 segments/patient), whereas 52 patients had dysfunctional myocardium with contractile enhancement by dobutamine echocardiography (4 +/- 2 segments/patient, p = 0.01). The extent of dysfunctional myocardium with contractile reserve appeared to correlate less closely with the total extent of viable dysfunctional myocardium identified by positron emission tomography than with the number of such segments associated with a pattern of perfusion-metabolism mismatch. CONCLUSIONS In patients with chronic ischemic left ventricular dysfunction, echocardiography can be used to identify enhancement in the contractile function of viable dysfunctional myocardium after infusion of low dose dobutamine. In this study, the presence and extent of such enhancement were relatively less than the values obtained from positron emission tomography.

Positron emission tomography scanning in the assessment of patients with lymphoma

Abstract