Longitudinal amyloid imaging using 11C-PiB: methodologic considerations.

Unlabelled: Several methods are in use for analyzing (11)C-Pittsburgh compound-B ((11)C-PiB) data. The objective of this study was to identify the method of choice for measuring longitudinal changes in specific (11)C-PiB binding.

Methods: Dynamic 90-min (11)C-PiB baseline and follow-up scans (interval, 30 ± 5 mo) were obtained for 7 Alzheimer disease (AD) patients, 11 patients with mild cognitive impairment (MCI), and 11 healthy controls.

Dopaminergic activity in Tourette syndrome and obsessive-compulsive disorder.

Tourette syndrome (TS) and obsessive-compulsive disorder (OCD) both are neuropsychiatric disorders associated with abnormalities in dopamine neurotransmission. Aims of this study were to quantify striatal D2/3 receptor availability in TS and OCD, and to examine dopamine release and symptom severity changes in both disorders following amphetamine challenge. Changes in [(11)C]raclopride binding potential (BP(ND)) were assessed using positron emission tomography before and after administration of d-amphetamine (0.

Effect of cardiac hybrid ¹⁵O-water PET/CT imaging on downstream referral for invasive coronary angiography and revascularization rate.

Aims: This study evaluates the impact of hybrid imaging on referral for invasive coronary angiography (ICA) and revascularization rates.

Methods And Results: A total of 375 patients underwent hybrid (15)O-water positron emission tomography (PET)/computed tomography (CT)-based coronary angiography (CTCA) imaging for the evaluation of coronary artery disease (CAD). Downstream treatment strategy within a 60-day period after hybrid PET/CTCA imaging for ICA referral and revascularization was assessed.

[11C]quinidine and [11C]laniquidar PET imaging in a chronic rodent epilepsy model: impact of epilepsy and drug-responsiveness.

Introduction: To analyse the impact of both epilepsy and pharmacological modulation of P-glycoprotein on brain uptake and kinetics of positron emission tomography (PET) radiotracers [(11)C]quinidine and [(11)C]laniquidar.

Methods: Metabolism and brain kinetics of both [(11)C]quinidine and [(11)C]laniquidar were assessed in naive rats, electrode-implanted control rats, and rats with spontaneous recurrent seizures. The latter group was further classified according to their response to the antiepileptic drug phenobarbital into "responders" and "non-responders".

Test-retest variability of various quantitative measures to characterize tracer uptake and/or tracer uptake heterogeneity in metastasized liver for patients with colorectal carcinoma.

Purpose: The aim of this study was to assess test-retest variability of various quantitative measures to characterize tracer uptake and/or tracer uptake heterogeneity.

Procedures: Two baseline whole-body 2-deoxy-2-[(18)F]fluoro-D-glucose positron emission tomography/computed tomography (CT) scans were acquired in 29 subjects with colorectal carcinoma. Whole liver volumes of interest (VOI) were defined manually on CT.

Evaluation of strategies towards harmonization of FDG PET/CT studies in multicentre trials: comparison of scanner validation phantoms and data analysis procedures.

Purpose: PET quantification based on standardized uptake values (SUV) is hampered by several factors, in particular by variability in PET acquisition settings and data analysis methods. Quantitative PET/CT studies acquired during a multicentre trial require harmonization of imaging procedures to maximize study power. The aims of this study were to determine which phantoms are most suitable for detecting differences in image quality and quantification, and which methods for defining volumes of interest (VOI) are least sensitive to these differences.

Pharmacokinetic analysis of [18F]FAZA in non-small cell lung cancer patients.

Purpose: [(18)F]Fluoroazomycin arabinoside (FAZA) is a positron emission tomography (PET) tracer developed to enable identification of hypoxic regions within a tumour. The aims of this study were to determine the optimal kinetic model along with validation of using alternatives to arterial blood sampling for analysing [(18)F]FAZA studies and to assess the validity of simplified analytical methods.

Methods: Dynamic 70-min [(18)F]FAZA PET/CT scans were obtained from nine non-small cell lung cancer patients.

11C-Acetate clearance as an index of oxygen consumption of the right myocardium in idiopathic pulmonary arterial hypertension: a validation study using 15O-labeled tracers and PET.

Unlabelled: Idiopathic pulmonary arterial hypertension (IPAH) results in increased right ventricular (RV) workload and oxygen demand. It has been shown that myocardial oxygen consumption (MVO2) of the hypertrophied right ventricle of IPAH patients can be measured using PET and (15)O-labeled tracers. This method is, however, not very suitable for routine clinical practice.

Toward prediction of efficacy of chemotherapy: a proof of concept study in lung cancer patients using [¹¹C]docetaxel and positron emission tomography.

Purpose: Pharmacokinetics of docetaxel can be measured in vivo using positron emission tomography (PET) and a microdose of radiolabeled docetaxel ([(11)C]docetaxel). The objective of this study was to investigate whether a [(11)C]docetaxel PET microdosing study could predict tumor uptake of therapeutic doses of docetaxel.

Experimental Design: Docetaxel-naïve lung cancer patients underwent 2 [(11)C]docetaxel PET scans; one after bolus injection of [(11)C]docetaxel and another during combined infusion of [(11)C]docetaxel and a therapeutic dose of docetaxel (75 mg·m(-2)).

Radiosynthesis and preclinical evaluation of [11C]prucalopride as a potential agonist PET ligand for the 5-HT4 receptor.

Background: Serotonin 5-HT4 receptor (5-HT4-R) agonists are potential therapeutic agents for enterokinetic and cognitive disorders and are marketed for treatment of constipation. The aim of this study was to develop an agonist positron emission tomography (PET) ligand in order to label the active G-protein coupled 5-HT4-R in peripheral and central tissues. For this purpose prucalopride, a high-affinity selective 5-HT4-R agonist, was selected.

Cerebral blood flow and glucose metabolism measured with positron emission tomography are decreased in human type 1 diabetes.

Subclinical systemic microvascular dysfunction exists in asymptomatic patients with type 1 diabetes. We hypothesized that microangiopathy, resulting from long-standing systemic hyperglycemia and hyperinsulinemia, may be generalized to the brain, resulting in changes in cerebral blood flow (CBF) and metabolism in these patients. We performed dynamic [(15)O]H2O and [(18)F]-fluoro-2-deoxy-d-glucose brain positron emission tomography scans to measure CBF and cerebral glucose metabolism (CMRglu), respectively, in 30 type 1 diabetic patients and 12 age-matched healthy controls after an overnight fast.

[11C]AF150(S), an agonist PET ligand for M1 muscarinic acetylcholine receptors.

Background: The M1 muscarinic acetylcholine receptor (M1ACh-R) is a G protein-coupled receptor that can occur in interconvertible coupled and uncoupled states. It is enriched in the basal ganglia, hippocampus, olfactory bulb, and cortical areas, and plays a role in motor and cognitive functions. Muscarinic M1 agonists are potential therapeutic agents for cognitive disorders.

Evaluation of the novel folate receptor ligand [18F]fluoro-PEG-folate for macrophage targeting in a rat model of arthritis.

Introduction: Detection of (subclinical) synovitis is relevant for both early diagnosis and monitoring of therapy of rheumatoid arthritis (RA). Previously, the potential of imaging (sub)clinical arthritis was demonstrated by targeting the translocator protein in activated macrophages using (R)-[11C]PK11195 and positron emission tomography (PET). Images, however, also showed significant peri-articular background activity.

In vivo imaging of the 18-kDa translocator protein (TSPO) with [18F]FEDAA1106 and PET does not show increased binding in Alzheimer's disease patients.

Purpose: Imaging the 18-kDa translocator protein (TSPO) is considered a potential tool for in vivo evaluation of microglial activation and neuroinflammation in the early stages of Alzheimer's disease (AD). ((R)-1-(2-chlorophenyl)-N-[(11)C]-methyl-N-(1-methylpropyl)-3-isoquinoline caboxamide ([(11)C]-(R)-PK11195) has been widely used for PET imaging of TSPO and, despite its low specific-to-nondisplaceable binding ratio, increased TSPO binding has been shown in AD patients. The high-affinity radioligand N-(5-fluoro-2-phenoxyphenyl)-N-(2-[(18)F]fluoroethyl-5-methoxybenzyl)acetamide ([(18)F]FEDAA1106) has been developed as a potential in vivo imaging tool for better quantification of TSPO binding.

Prognostic impact of [18F]fluorothymidine and [18F]fluoro-D-glucose baseline uptakes in patients with lung cancer treated first-line with erlotinib.

Unlabelled: 3'-deoxy-3'-[(18)F]fluoro-L-thymidine (FLT) and 2'-deoxy-2'-[(18)F]fluoro-D-glucose (FDG) are used to visualize proliferative and metabolic activity of tumors. In this study we aimed at evaluating the prognostic value of FLT and FDG uptake measured by positron emission tomography (PET) in patients with metastatic non-small cell lung cancer (NSCLC) prior to systemic therapy with erlotinib. FLT and FDG maximum standardized uptake (SUVmax) values per patient were analyzed in 40 chemotherapy naive patients with advanced NSCLC (stage IV) before treatment with erlotinib.

Differential effect of APOE genotype on amyloid load and glucose metabolism in AD dementia.

Objective: To examine the relationships between apolipoprotein E (APOE) ε4 dose and in vivo distributions of both fibrillary amyloid burden and glucose metabolism in the same Alzheimer disease dementia patients, selected for abnormal amyloid imaging.

Methods: Twenty-two APOE ε4 negative, 40 heterozygous, and 22 homozygous Alzheimer disease dementia patients underwent dynamic (90 minutes) [(11)C]Pittsburgh compound B (PIB) and static [(18)F]fluorodeoxyglucose (FDG) PET scans. Parametric nondisplaceable binding potential images of [(11)C]PIB and standardized uptake value ratio images of [(18)F]FDG were generated using cerebellar gray matter as reference tissue.

Amyloid and its association with default network integrity in Alzheimer's disease.

The purpose of this study was to investigate the association between functional connectivity and β-amyloid depositions in the default mode network (DMN) in Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and healthy elderly. Twenty-five patients with AD, 12 patients with MCI, and 18 healthy controls were included in the study. Resting-state functional magnetic resonance imaging was used to assess functional connectivity in the DMN.

Hybrid imaging using quantitative H215O PET and CT-based coronary angiography for the detection of coronary artery disease.

Unlabelled: Hybrid imaging using PET in conjunction with CT-based coronary angiography (PET/CTCA) enables near-simultaneous quantification of myocardial blood flow (MBF) and anatomical evaluation of coronary arteries. CTCA is an excellent imaging modality to rule out obstructive coronary artery disease (CAD), but functional assessment is warranted in the presence of a CTCA-observed stenosis because the specificity of CTCA is relatively low. Quantitative H(2)(15)O PET/CTCA may yield complementary information and enhance diagnostic accuracy.

Limbic and motor circuits involved in symmetry behavior in Tourette's syndrome.

Objective: The need for symmetry and ordering objects related to a "just right"-feeling is a common symptom in Tourette's syndrome (TS) and resembles symmetry behavior in obsessive-compulsive disorder, but its pathophysiology is unknown. We used a symptom provocation paradigm to investigate the neural correlates of symmetry behavior in TS and hypothesized the involvement of frontal-striatal and limbic brain areas.

Methods: Pictures of asymmetrically and symmetrically arranged objects were presented in randomized blocks (4 blocks of each condition) to 14 patients with TS and 10 matched healthy controls (HC).

Cerebral blood flow and glucose metabolism in healthy volunteers measured using a high-resolution PET scanner.

Background: Positron emission tomography (PET) allows for the measurement of cerebral blood flow (CBF; based on [15O]H2O) and cerebral metabolic rate of glucose utilization (CMRglu; based on [18 F]-2-fluoro-2-deoxy-d-glucose ([18 F]FDG)). By using kinetic modeling, quantitative CBF and CMRglu values can be obtained. However, hardware limitations led to the development of semiquantitive calculation schemes which are still widely used.

Impact of molecular imaging on the diagnostic process in a memory clinic.

Background: [(11)C]Pittsburgh compound B ([(11)C]PIB) and [(18)F]-2-fluoro-2-deoxy-D-glucose ([(18)F]FDG) PET measure fibrillar amyloid-β load and glucose metabolism, respectively. We evaluated the impact of these tracers on the diagnostic process in a memory clinic population.

Methods: One hundred fifty-four patients underwent paired dynamic [(11)C]PIB and static [(18)F]FDG PET scans shortly after completing a standard dementia screening.

Altered GABAA receptor density and unaltered blood-brain barrier transport in a kainate model of epilepsy: an in vivo study using 11C-flumazenil and PET.

Unlabelled: The aim of the present study was to investigate if flumazenil blood-brain barrier transport and binding to the benzodiazepine site on the γ-aminobutyric acid A (GABA(A)) receptor complex is altered in an experimental model of epilepsy and subsequently to study if changes in P-glycoprotein (P-gp)-mediated efflux of flumazenil at the blood-brain barrier may confound interpretation of (11)C-flumazenil PET in epilepsy.

Methods: The transport of flumazenil across the blood-brain barrier and the binding to the benzodiazepine site on the GABA(A) receptors in 5 different brain regions was studied and compared between controls and kainate-treated rats, a model of temporal lobe epilepsy, with and without tariquidar pretreatment. In total, 29 rats underwent 2 consecutive (11)C-flumazenil PET scans, each one lasting 30 min.