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Early applications of positron emission tomography (PET) in psychiatry sought to identify derangements of cerebral blood flow and metabolism. The need for more specific neurochemical imaging probes was soon evident, and these probes initially targeted the sites of action of neuroleptic (dopamine D

With the emergence of positron emission tomography (PET) in the late 1970s, psychiatry had access to a tool capable of non-invasive assessment of human brain function. Early applications in psychiatry focused on identifying characteristic brain blood flow and metabolic derangements using radiotracers such as [

Introduction Equol, a metabolite of a soy isoflavone transformed by the gut microbiome, is anti‐oxidant and anti‐amyloidogenic. We assessed the associations of equol with white matter lesion normalized to total brain volume (WML%) and amyloid beta (Aβ) deposition. Methods From 2016 to 2018, 91 cognitively normal elderly Japanese aged 75 to 89 underwent brain magnetic resonance imaging and positron emission tomography using 11C‐Pittsburgh compound‐B. Serum equol was measured using stored samples from 2008 to 2012. Equol producers were defined as individuals with serum levels >0. Producers were further divided into high (> the median) and low (≤ the median) producers. Results The median (interquartile range) WML% was 1.10 (0.59 to 1.61); 24.2% were Aβ positive, and 51% were equol producers. Equol‐producing status (non‐producers, low and high) was significantly inversely associated with WML%: 1.19, 0.89, and 0.58, respectively (trend P

Introduction We sought to establish the relationships between standard postmortem measures of AD neuropathology and antemortem [ 11 C]PIB–positron emission tomography ([ 11 C]PIB-PET) analyzed with the Centiloid (CL) method, a standardized scale for Aβ-PET quantification. Methods Four centers contributed 179 participants encompassing a broad range of clinical diagnoses, PET data, and autopsy findings. Results CL values increased with each CERAD neuritic plaque score increment (median −3 CL for no plaques and 92 CL for frequent plaques) and nonlinearly with Thal Aβ phases (increases were detected starting at phase 2) with overlap between scores/phases. PET-pathology associations were comparable across sites and unchanged when restricting the analyses to the 56 patients who died within 2 years of PET. A threshold of 12.2 CL detected CERAD moderate-to-frequent neuritic plaques (area under the curve = 0.910, sensitivity = 89.2%, specificity = 86.4%), whereas 24.4 CL identified intermediate-to-high AD neuropathological changes (area under the curve = 0.894, sensitivity = 84.1%, specificity = 87.9%). Discussion Our study demonstrated the robustness of a multisite Centiloid [ 11 C]PIB-PET study and established a range of pathology-based CL thresholds.

Objective Recent studies have shown that positron emission tomography (PET) tracer AV-1451 exhibits high binding affinity for paired helical filament (PHF)-tau pathology in Alzheimer's brains. However, the ability of this ligand to bind to tau lesions in other tauopathies remains controversial. Our goal was to examine the correlation of in vivo and postmortem AV-1451 binding patterns in three autopsy-confirmed non-Alzheimer tauopathy cases. Methods We quantified in vivo retention of [F-18]-AV-1451 and performed autoradiography, [H-3]-AV-1451 binding assays, and quantitative tau measurements in postmortem brain samples from two progressive supranuclear palsy (PSP) cases and a MAPT P301L mutation carrier. They all underwent [F-18]-AV-1451 PET imaging before death. Results The three subjects exhibited [F-18]-AV-1451 in vivo retention predominantly in basal ganglia and midbrain. Neuropathological examination confirmed the PSP diagnosis in the first two subjects; the MAPT P301L mutation carrier had an atypical tauopathy characterized by grain-like tau-containing neurites in gray and white matter with heaviest burden in basal ganglia. In all three cases, autoradiography failed to show detectable [F-18]-AV-1451 binding in multiple brain regions examined, with the exception of entorhinal cortex (reflecting incidental age-related neurofibrillary tangles) and neuromelanin-containing neurons in the substantia nigra (off-target binding). The lack of a consistent significant correlation between in vivo [F-18]-AV-1541 retention and postmortem in vitro binding and tau measures in these cases suggests that this ligand has low affinity for tau lesions primarily made of straight tau filaments. Interpretation AV-1451 may have limited utility for in vivo selective and reliable detection of tau aggregates in these non-Alzheimer tauopathies. ANN NEUROL 2017;81:117–128

Author(s): Bailer, Ursula F; Price, Julie C; Meltzer, Carolyn C; Wagner, Angela; Mathis, Chester A; Gamst, Anthony; Kaye, Walter H | Abstract: ObjectiveIndividuals with anorexia nervosa (AN) have anxious and inhibited temperaments with high concern for consequences. Studies using either positron emission tomography (PET) or functional magnetic resonance imaging (fMRI) suggest involvement of the middle and dorsal caudate (DC) in individuals recovered (REC) from AN. For example, dopamine (DA) D2/D3 receptor binding in the middle caudate and DC was associated with anxiety and harm avoidance, and blood-oxygen-level-dependent (BOLD) response in the DC was positively related to trait anxiety. It has not been shown yet whether BOLD response in individuals REC from AN was related to DA function.MethodsPost-hoc correlation analyses between the PET and fMRI studies by correlating D2/D3 binding in striatal regions and BOLD signal in the anteroventral striatum (AVS) and DC for wins and losses respectively in 12 individuals REC from AN.ResultsIndividuals REC from AN with the greatest BOLD response in the DC in a monetary choice task had higher middle caudate D2/D3 binding, and greater anxiety and/or harm avoidance.DiscussionThough preliminary, these findings suggest that increased dorsal striatal D2/D3 binding is associated with enhanced cognitive response to feedback, potentially related to anxious anticipation of consequences. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:593-596).

Objective To examine region- and substrate-specific autoradiographic and in vitro binding patterns of positron emission tomography tracer [F-18]-AV-1451 (previously known as T807), tailored to allow in vivo detection of paired helical filament-tau–containing lesions, and to determine whether there is off-target binding to other amyloid/non-amyloid proteins. Methods We applied [F-18]-AV-1451 phosphor screen autoradiography, [F-18]-AV-1451 nuclear emulsion autoradiography, and [H-3]-AV-1451 in vitro binding assays to the study of postmortem samples from patients with a definite pathological diagnosis of Alzheimer disease, frontotemporal lobar degeneration–tau, frontotemporal lobar degeneration–transactive response DNA binding protein 43 (TDP-43), progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy, cerebral amyloid angiopathy and elderly controls free of pathology. Results Our data suggest that [F-18]-AV-1451 strongly binds to tau lesions primarily made of paired helical filaments in Alzheimer brains (eg, intraneuronal and extraneuronal tangles and dystrophic neurites), but does not seem to bind to a significant extent to neuronal and glial inclusions mainly composed of straight tau filaments in non-Alzheimer tauopathy brains or to lesions containing β-amyloid, α-synuclein, or TDP-43. [F-18]-AV-1451 off-target binding to neuromelanin- and melanin-containing cells and, to a lesser extent, to brain hemorrhagic lesions was identified. Interpretation Our data suggest that [F-18]-AV-1451 holds promise as a surrogate marker for the detection of brain tau pathology in the form of tangles and paired helical filament-tau–containing neurites in Alzheimer brains but also point to its relatively lower affinity for lesions primarily made of straight tau filaments in non-Alzheimer tauopathy cases and to the existence of some [F-18]-AV-1451 off-target binding. These findings provide important insights for interpreting in vivo patterns of [F-18]-AV-1451 retention. Ann Neurol 2015 Ann Neurol 2015;78:Ann Neurol 2015;78:679–696

© 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved. Introduction This article reviews the work done in the Alzheimer's Disease Neuroimaging Initiative positron emission tomography (ADNI PET) core over the past 5 years, largely concerning techniques, methods, and results related to amyloid imaging in ADNI. Methods The PET Core has used [18F]florbetapir routinely on ADNI participants, with over 1600 scans available for download. Four different laboratories are involved in data analysis, and have examined factors such as longitudinal florbetapir analysis, use of [18F]fluorodeoxyglucose (FDG)-PET in clinical trials, and relationships between different biomarkers and cognition. Results Converging evidence from the PET Core has indicated that cross-sectional and longitudinal florbetapir analyses require different reference regions. Studies have also examined the relationship between florbetapir data obtained immediately after injection, which reflects perfusion, and FDG-PET results. Finally, standardization has included the translation of florbetapir PET data to a centiloid scale. Conclusion The PET Core has demonstrated a variety of methods for the standardization of biomarkers such as florbetapir PET in a multicenter setting.

In Down syndrome (DS), the overproduction of amyloid precursor protein is hypothesized to predispose young adults to early expression of Alzheimer-like neuropathology.PET imaging with carbon 11-labeled Pittsburgh compound B examined the pattern of amyloid-β deposition in 68 nondemented adults with DS (30-53 years) to determine the relationship between deposition and normal aging. Standard uptake value ratio (SUVR) images were created with cerebellar gray matter as the reference region.Multiple linear regression revealed slight but highly significant (corrected P.05) positive correlations between SUVR and age. The striatum showed the strongest correlation, followed by precuneus, parietal cortex, anterior cingulate, frontal cortex, and temporal cortex.There is an age-related amyloid-β deposition in the DS population, but as a pattern of elevated cortical retention becomes apparent, the correlation of SUVR with age ceases to be significant. Factors unrelated to aging may drive an increase in deposition during early Alzheimer's disease pathogenesis.

Objective This study examined amyloid-β (Aβ) deposition in 190 nondemented subjects aged ≥82 years to determine the proportion of Aβ-positive scans and associations with cognition, apolipoprotein E (APOE) status, brain volume, and Ginkgo biloba (Gb) treatment. Methods Subjects who agreed to participate had a brain magnetic resonance imaging and positron emission tomography scan with 11C-labeled Pittsburgh compound B (PiB) following completion of a Gb treatment clinical trial. The youngest subject in this imaging study was 82 years, and the mean age of the subjects was 85.5 years at the time of the scans; 152 (80%) were cognitively normal, and 38 (20%) were diagnosed with mild cognitive impairment (MCI) at the time of the PiB study. Results A high proportion of the cognitively normal subjects (51%) and MCI subjects (68%) were PiB-positive. The APOE*4 allele was more prevalent in PiB-positive than in PiB-negative subjects (30% vs 6%). Measures of memory, language, and attentional functions were worse in PiB-positive than in PiB-negative subjects, when both normal and MCI cases were analyzed together; however, no significant associations were observed within either normal or MCI subject groups alone. There was no relationship between Gb treatment and Aβ deposition as determined by PiB. Interpretation The data revealed a 55% prevalence of PiB positivity in nondemented subjects age >80 years and 85% PiB positivity in the APOE*4 nondemented elderly subjects. The findings also showed that long-term exposure to Gb did not affect the prevalence of cerebral Aβ deposition. ANN NEUROL 2013;73:751–761

The development of positron emission tomography (PET) radioligands for the non-invasive imaging of amyloid-β plaque burden has been the focus of intense research efforts over the last decade. A variety of structural backbones have been investigated and several radiolabeled molecules have been evaluated in phase I (and later) clinical studies. These efforts have been driven by the desire not only to develop a suitable diagnostic imaging agent but also to develop a means to evaluate potential therapies for Alzheimer's disease. This review focuses on the development of these ligands, as well as the radiochemistry and current regulatory status of these PET radioligands. Particular attention is given to those ligands that have progressed to the later stages of drug development (phase II/III clinical trial studies) or approved New Drug Application status.

Down syndrome (DS) is one of the most common causes of intellectual disability. Although DS accounts for only 15% of all individuals with intellectual disabilities, adults with DS account for approximately 60% of individuals with intellectual disabilities and Alzheimer's disease. This is thought to be because of overproduction of the β-amyloid (Aβ) protein due to trisomy for the Aβ precursor protein gene on chromosome 21. Pittsburgh compound B (PiB) is a noninvasive in vivo positron emission tomography tracer used to image amyloid deposition in living humans. Studies using PiB have shown an age-dependent asymptomatic amyloid deposition in more than 20% of the cognitively normal elderly population. Presymptomatic carriers of presenilin (PS-1) and Aβ precursor protein gene mutations who are destined to develop Alzheimer's disease also show preclinical amyloid deposition. This report describes a pilot study involving the use of PiB in seven adults with DS (age: 20–44 years). Compared with objective cutoffs for amyloid positivity in older non-DS cognitively normal control subjects, only two of the seven DS subjects (age: 38 and 44 years) showed increased PiB retention. The remaining five subjects aged between 20 and 35 years showed no detectable increase in PiB retention. Interestingly, the two subjects who showed elevated PiB retention showed a striatal-predominant pattern similar to that previously reported for PS-1 mutation carriers. These results demonstrate the feasibility of conducting PiB positron emission tomography scanning in this special population, and suggest a link between Aβ overproduction and early striatal deposition of fibrillar Aβ.

Positron emission tomography (PET) studies performed with [(11) C]raclopride have consistently reported lower binding to D(2/3) receptors and lower amphetamine-induced dopamine (DA) release in cocaine abusers relative to healthy controls. A limitation of these studies that were performed with D(2/3) antagonist radiotracers such as [(11) C]raclopride is the failure to provide information that is specific to D(2/3) receptors configured in a state of high affinity for the agonists (i.e., D(2/3) receptors coupled to G-proteins, D(2/3 HIGH) ). As the endogenous agonist DA binds with preference to D(2/3 HIGH) relative to D(2/3 LOW) receptors (i.e., D(2/3) receptors uncoupled to G-proteins) it is critical to understand the in vivo status of D(2/3 HIGH) receptors in cocaine dependence. Thus, we measured the available fraction of D(2/3) (HIGH) receptors in 10 recently abstinent cocaine abusers (CD) and matched healthy controls (HC) with the D(2/3) antagonist and agonist PET radiotracers [(11) C]raclopride and [(11) C]NPA.[(11) C]raclopride and [(11) C]NPA binding potential (BP) (BP(ND) ) in the striatum were measured with kinetic analysis using the arterial input function. The available fraction of D(2/3 HIGH) receptors, i.e., % R(HIGH) available = D(2/3 HIGH) /(D(2/3 HIGH) + D(2/3 LOW) ) was then computed as the ratio of [(11) C]NPA BP(ND) /[(11) C]raclopride BP(ND) .No differences in striatal [(11) C]NPA BP(ND) (HC = 1.00 ± 0.17; CD = 0.97 ± 0.17, P = 0.67) or available % R(HIGH) (HC = 39% ± 5%; CD = 41% ± 5%, P = 0.50) was observed between cocaine abusers and matched controls.The results of this [(11) C]NPA PET study do not support alterations in D(2/3 HIGH) binding in the striatum in cocaine dependence.

In vivo amyloid imaging with positron emission tomography (PET) allows longitudinal study of Aβ deposition in an individual and should provide unique information on the relationship between Aβ and cognitive decline. Although it is likely that Aβ plays a fundamental role in the development of dementia of the Alzheimer type (DAT),1 postmortem studies have not consistently demonstrated a relationship between the density of amyloid plaques and the severity of dementia.2–5 The time course of plaque formation is unclear. Studies comparing the plaque density at brain biopsy in DAT patients to that assessed in those same patients at postmortem several years later found little change in the majority of patients, but these studies had few participants.6–9 An additional perplexing postmortem observation is the high prevalence of amyloid plaques in the normal elderly. It has been postulated that this represents preclinical DAT, but this cannot be proven by autopsy-based studies. In vivo Aβ imaging provides the means to address these questions through longitudinal observation. Cross-sectional [11C]Pittsburgh compound B (PiB) PET studies have shown a robust difference between the retention patterns in DAT patients and healthy controls (HCs).10,11 In agreement with postmortem data,2 approximately 20 to 30% of elderly HC subjects show some degree of increased cortical PiB retention, predominantly in the prefrontal cortex and posterior cingulate/precuneus areas.10,12–14 Polymorphism of the apolipoprotein E (ApoE) allele is among the most consistent genetic risk factors associated with sporadic DAT, and its presence is thought to result in an earlier age of onset.15,16 Examination of ApoE e4 allele status revealed that healthy e4 carriers present with significantly higher PiB retention than e4 noncarriers and show increased retention at an earlier age, further emphasizing the crucial role that ApoE plays in the metabolism of Aβ.10,17–20 Recently, several studies have found significant increases in PiB retention in some individuals over 1 to 2 years, but no overall increase in mean PiB retention in groups of subjects with DAT or mild cognitive impairment (MCI). These studies did report a higher conversion rate from MCI to DAT in those with high PiB retention, despite a lack of significant change in PiB retention in those who progressed.21–24 The objectives of this study were to quantify the progression of Aβ plaque formation in the brain over time with PiB PET in a large number of individuals and to correlate Aβ plaque burden at baseline and follow-up with clinical measures of disease severity, cognitive decline, and ApoE status.

Objective Because altered serotonin (5-HT) function appears to persist after recovery from bulimia nervosa (RBN), we investigated the 5-HT1A receptor, which could contribute to regulation of appetite, mood, impulse control, or the response to antidepressants. Method Thirteen RBN individuals were compared to 21 healthy control women (CW) using positron emission tomography and [carbonyl-11C]WAY100635 ([11C]WAY). Results RBN had a 23–34% elevation of [11C]WAY binding potential (BP)P in subgenual cingulate, mesial temporal, and parietal regions after adjustments for multiple comparisons. For CW, [11C]WAY BPP was related negatively to novelty seeking, whereas for RBN, [11C]WAY BPP was related positively to harm avoidance and negatively related to sensation seeking. Discussion Alterations of 5-HT1A receptor function may provide new insight into efficacy of 5-HT medication in BN, as well as symptoms such as the ability to inhibit or self-control the expression of behaviors related to stimulus seeking, aggression, and impulsivity. © 2010 by Wiley Periodicals, Inc. Int J Eat Disord 2011

In a recent PET study, we demonstrated the ability to measure amphetamine-induced DA release in the human cortex with the relatively high affinity dopamine D2/3 radioligand [11C]FLB 457 (Narendran et al., [2009] Synapse 63:447–461). The aim of this study was to evaluate the reproducibility and reliability of [11C]FLB 457 in the same imaging paradigm we used to measure amphetamine-induced DA transmission. Six healthy human subjects (three males/three females) were studied twice with [11C]FLB 457, once at baseline and again 3 h following the end of the baseline scan. D2/3 receptor binding parameters were estimated using a two-tissue compartment kinetic analysis in the cortical regions of interest and cerebellum (reference region). The test–retest variability and intraclass correlation coefficient were assessed for distribution volume (VT), binding potential relative to plasma concentration (BPP), and binding potential relative to nondisplaceable uptake (BPND) of [11C]FLB 457. The test–retest variability of [11C]FLB 457 VT, BPP, and BPND were ≤15%, consistent with the published test–retest variability for this ligand in other brain regions (Sudo et al., [2001] Nucl Med Commun 22:1215–1221; Vilkman et al., [2000] Eur J Nucl Med 27:1666–1673). In addition, no significant decrease in [11C]FLB 457 BPND was observed in the second scan compared to the first one. This suggests that the contribution of carryover mass of [11C]FLB 457 to the measured reduction in [11C]FLB 457 BPND following amphetamine was relatively low. These data support the further validation of [11C]FLB 457 as a tool to measure amphetamine-induced dopamine release in the human cortex. Synapse 65:35–40, 2011. © 2010 Wiley-Liss, Inc.

Background This is a progress report of the Alzheimer's Disease Neuroimaging Initiative (ADNI) positron emission tomography (PET) Core. Methods The Core has supervised the acquisition, quality control, and analysis of longitudinal [ 18 F]fluorodeoxyglucose PET (FDG-PET) data in approximately half of the ADNI cohort. In an "add on" study, approximately 100 subjects also underwent scanning with [ 11 C] Pittsburgh compound B PET for amyloid imaging. The Core developed quality control procedures and standardized image acquisition by developing an imaging protocol that has been widely adopted in academic and pharmaceutical industry studies. Data processing provides users with scans that have identical orientation and resolution characteristics despite acquisition on multiple scanner models. The Core labs have used many different approaches to characterize differences between subject groups (Alzheimer's disease, mild cognitive impairment, controls), to examine longitudinal change over time in glucose metabolism and amyloid deposition, and to assess the use of FDG-PET as a potential outcome measure in clinical trials. Results ADNI data indicate that FDG-PET increases statistical power over traditional cognitive measures, might aid subject selection, and could substantially reduce the sample size in a clinical trial. Pittsburgh compound B PET data showed expected group differences, and identified subjects with significant annual increases in amyloid load across the subject groups. The next activities of the PET core in ADNI will entail developing standardized protocols for amyloid imaging using the [ 18 F]-labeled amyloid imaging agent AV45, which can be delivered to virtually all ADNI sites. Conclusions ADNI has demonstrated the feasibility and utility of multicenter PET studies and is helping to clarify the role of biomarkers in the study of aging and dementia.

Objective Cerebrovascular deposition of β-amyloid (cerebral amyloid angiopathy [CAA]) is a major cause of hemorrhagic stroke and a likely contributor to vascular cognitive impairment. We evaluated positron emission tomographic imaging with the β-amyloid–binding compound Pittsburgh Compound B (PiB) as a potential noninvasive method for detection of CAA. We hypothesized that amyloid deposition would be observed with PiB in CAA, and based on the occipital predilection of CAA pathology and associated hemorrhages, that specific PiB retention would be disproportionately greater in occipital lobes. Methods We compared specific cortical PiB retention in 6 nondemented subjects diagnosed with probable CAA with 15 healthy control subjects and 9 patients with probable Alzheimer's disease (AD). Results All CAA and AD subjects were PiB-positive, both by distribution volume ratio measurements and by visual inspection of positron emission tomographic images. Global cortical PiB retention was significantly increased in CAA (distribution volume ratio 1.18 ± 0.06) relative to healthy control subjects (1.04 ± 0.10; p = 0.0009), but was lower in CAA than in AD subjects (1.41 ± 0.17; p = 0.002). The occipital-to-global PiB ratio, however, was significantly greater in CAA than in AD subjects (0.99 ± 0.07 vs 0.86 ± 0.05; p = 0.003). Interpretation We conclude that PiB-positron emission tomography can detect cerebrovascular β-amyloid and may serve as a method for identifying the extent of CAA in living subjects. Ann Neurol 2007

Activated microglia are an important feature of many neurological diseases and can be imaged in vivo using 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195), a ligand that binds the peripheral benzodiazepine receptor (PBR). N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl) acetamide (DAA1106) is a new PBR-specific ligand that has been reported to bind to PBR with higher affinity compared with PK11195. We hypothesized that this high-affinity binding of DAA1106 to PBR will enable better delineation of microglia in vivo using positron emission tomography. [3H]DAA1106 showed higher binding affinity compared with [3H](R)-PK11195 in brain tissue derived from normal rats and the rats injected intrastriatally with 6-hydroxydopamine or lipopolysaccharide at the site of the lesion. Immunohistochemistry combined with autoradiography in brain tissues as well as correlation analyses showed that increased [3H]DAA1106 binding corresponded mainly to activated microglia. Finally, ex vivo autoradiography and positron emission tomography imaging in vivo showed greater retention of [11C]DAA1106 compared with [11C](R)-PK11195 in animals injected with either lipopolysaccaride or 6-hydroxydopamine at the site of lesion. These results indicate that DAA1106 binds with higher affinity to microglia in rat models of neuroinflammation when compared with PK11195, suggesting that [11C]DAA1106 may represent a significant improvement over [11C](R)-PK11195 for in vivo imaging of activated microglia in human neuroinflammatory disorders.

Abnormalities of regional cerebral blood flow (rCBF) have been found in individuals who are ill with anorexia (AN) or bulimia nervosa (BN). Little is known about whether rCBF normalizes after recovery from AN and BN.Eighteen control women (CW), 10 recovered restricting type AN, 8 recovered AN with a binging history, and 9 recovered BN participants without a history of AN were studied using positron emission tomography and [(15)O]water in order to assess rCBF.Partial volume corrected rCBF values in cortical and subcortical brain regions were similar between groups. Neither current body mass index nor age correlated with rCBF values.The results from this study indicate that rCBF normalizes with long-term recovery. Thus, altered rCBF is unlikely to confound functional imaging studies in AN or BN after recovery.

Carboxylic acid derivatives of the amyloid-binding dye Congo red do not enter the brain well and are thus unable to serve as in vivo amyloid-imaging agents. A neutral amyloid probe, (E,E)-1-(3′,4′-dihydroxystyryl)-4-(3′-methoxy-4′-hydroxystyryl)benzene (3), devoid of any carboxylate groups has been designed and synthesized via a 12-step reaction sequence with a total yield of 30%. The unsymmetric compound 3 has also been labelled with C-11 via [11C]methyl iodide ([11C]CH3I) methylation of a symmetric 4,4′-dimesyl protected precursor followed by deprotection. Preliminary evaluation indicated that compound 3 selectively stained plaques and neurofibrillary tangles in post-mortem AD brain, and exhibited good binding affinity (Ki=38±8 nM) for Aβ(1–40) fibrils in vitro. In vivo pharmacokinetic studies indicated that [11C]3 exhibited higher brain uptake than its carboxylic acid analogs and good clearance from normal control mouse brain. [11C]3 also exhibited specific in vivo binding to pancreatic amyloid deposits in the NOR-beta transgenic mouse model. These results justify further investigation of 3 and similar derivatives as surrogate markers for in vivo quantitation of amyloid deposits. Copyright © 2002 John Wiley & Sons, Ltd.