Igor D GrachevTeva Pharmaceutical Industries Ltd. | TEVA · Department of Research and Development
Igor D Grachev
MD, PhD
About
102
Publications
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Introduction
Additional affiliations
June 2014 - October 2014
Novartis Consumer Health, Inc
Position
- Clinical Development and Medical Affairs Lead (Consultant)
Publications
Publications (102)
In vivo imaging of brain β-amyloid, a hallmark of Alzheimer disease, may assist in the clinical assessment of suspected Alzheimer disease.
To determine the sensitivity and specificity of positron emission tomography imaging with flutemetamol injection labeled with radioactive fluorine 18 to detect β-amyloid in the brain using neuropathologically de...
Diagnostic effectiveness of Ioflupane I 123 injection (DaTSCAN™, DaTscan™, or [123I]FP-CIT or ioflupane [(123)I]) SPECT imaging, was assessed in patients with clinically uncertain parkinsonian syndrome (CUPS).
We investigated the association between subject's Hoehn & Yahr (H&Y) stage, Mini-Mental State Examination (MMSE), age, and motor symptom sub...
Objectives To pool clinical trials of similar design to assess overall sensitivity and specificity of ioflupane I123 injection (DaTSCAN or ioflupane (123I)) to detect or exclude a striatal dopaminergic deficit disorder (SDDD), such as parkinsonian syndrome and dementia with Lewy bodies.
Design Pooled analysis of three phase 3 and one phase 4 clinic...
11C-SCH442416 was reported in preclinical studies with rodents and primates to be the first nonxanthine radioligand suitable for the in vivo imaging of adenosine A2A receptors with positron emission tomography (PET). The aim of the present work was to investigate the suitability of 11C-SCH442416 for the in vivo quantification of A2A receptors in hu...
11C-SCH442416 was reported in preclinical studies with rodents and primates to be the first nonxanthine radioligand suitable for the in vivo imaging of adenosine A2A receptors with positron emission tomography (PET). The aim of the present work was to investigate the suitability of 11C-SCH442416 for the in vivo quantification of A2A receptors in hu...
Ioflupane is an analog of cocaine that binds reversibly with high affinity to the dopamine transporter (DaT) protein, a marker for presynaptic terminals in dopaminergic nigrostriatal neurons. Ioflupane (123)I Injection is also known as DaTscan or DaTSCAN ((123)I-ioflupane is also called (123)I-2-β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl)no...
Unlabelled:
Establishing an early, accurate diagnosis is fundamental for appropriate clinical management of patients with movement disorders or dementia. Ioflupane (123)I Injection (DaTscan, (123)I-ioflupane) is an important adjunct to support the clinical diagnosis. Understanding individual-reader diagnostic performance of (123)I-ioflupane in a v...
Background: To determine the diagnostic effectiveness of (123I) ioflupane injection (DaTscan™) in patients with early, clinically uncertain parkinsonian syndrome (CUPS), 122 clinical trial subjects with CUPS who had experienced motor and non-motor signs and symptoms up to 5 years prior to enrolment underwent DaTscan imaging.
AD: Alzheimer’s Disease; DLB: Dementia with Lewy Bodies; ET: Essential Tremor; MSA: Multiple System Atrophy; PD: Parkinson’s Disease; PS: Parkinsonian Syndrome; PSP: Progressive Supranuclear Palsy; SPECT: Single-Photon Emission Computed Tomography; SWEDDs: Scans Without Evidence of Dopminergic Deficit
Introduction:
PET imaging of amyloid-β (Aβ) in vivo holds promise for aiding in earlier diagnosis and intervention in Alzheimer's disease (AD) and mild cognitive impairment. AD-like Aβ pathology is a common comorbidity in patients with idiopathic normal pressure hydrocephalus (iNPH). Fifty patients with iNPH needing ventriculo-peritoneal shunting...
Parkinson's disease (PD), the second-most common neurodegenerative disease, is characterized by motor and nonmotor symptoms. PD is often misdiagnosed; inappropriate treatment due to misdiagnosis has undesired consequences, as does delayed diagno- sis. Unfortunately, most people with PD receive a diagnosis only after motor symptoms have emerged, by...
Unlabelled:
BACKGOUND/OBJECTIVE: To determine the level of association between uptake of the amyloid positron emission tomography (PET) imaging agent [(18)F]flutemetamol and the level of amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical region biopsy site.
Methods:
Seventeen patients with probable normal...
Background and purposeThis study determined the correlation between uptake of the amyloid positron emission tomography (PET) imaging agent [18F]flutemetamol and amyloid-β measured by immunohistochemical and histochemical staining in a frontal cortical biopsy. Methods
Fifteen patients with possible normal pressure hydrocephalus (NPH) and previous br...
The diagnosis of movement disorders including Parkinson's disease (PD) and essential tremor is determined through clinical assessment. The difficulty with diagnosis of early PD has been highlighted in several recent clinical trials. Studies have suggested relatively high clinical diagnostic error rates for PD and essential tremor. This review was u...
Molecular imaging techniques developed to 'visualize' amyloid in vivo represent a major achievement in Alzheimer's disease (AD) research. This pooled analysis of four studies determined the level of association between uptake of the fibrillar amyloid b positron emission tomography (PET) imaging agent [ 18 F]flutemetamol (Pittsburgh Compound B analo...
Molecular imaging techniques developed to ‘visualize’ amyloid in vivo represent a major achievement in Alzheimer’s disease (AD) research. This pooled analysis of four studies determined the level of association between uptake of the fibrillar amyloid β positron emission tomography (PET) imaging agent [18F]flutemetamol (Pittsburgh Compound B analog...
Purpose:
The primary objectives of this study were to assess the safety of [(18)F]flutemetamol injection and determine the level of association between the quantitative estimates of brain uptake of [(18)F]flutemetamol and the quantitative immunohistochemical (IHC) estimates of amyloid levels in cerebral cortex biopsies obtained during shunt placem...
Preladenant (SCH420814, MK-3814) is a highly selective orally bioavailable non-methylxanthine adenosine 2A (A(2A) ) receptor antagonist under investigation for the treatment for Parkinson's disease. This study evaluated the safety, tolerability and pharmacokinetics of preladenant at single and multiple doses for the first time in humans.
These were...
Background:
An accurate diagnosis is important for timely and adequate treatment in patients with clinically uncertain parkinsonian syndrome (CUPS).
Objective:
The objective of this study was to assess safety and changes in clinical management, diagnosis and quality of life (QoL) at 4 and 12 weeks following DaTscan (ioflupane [(123)I] injection)...
http://www.ncbi.nlm.nih.gov/pubmed/22508283#
Realizing that 60% to 80% of dopaminergic nigrostriatal neurons are nonfunctional at the time of clinical diagnosis, there is an emerging consensus that disease-modifying treatments should be initiated in the earliest stages of Parkinson's disease (PD). To date, clinical trial designs and metrics in PD have been focused on motor symptoms as the cor...
This study assessed the impact of DaTscan on clinical management, diagnosis, confidence of diagnosis (CoD), quality of life (QoL), health resource use (HRU) and safety during a 1-year follow-up in patients with clinically uncertain parkinsonian syndromes (CUPS).
A total of 19 university hospital centres in Europe and the USA participated in this op...
The aim of this study was to evaluate the effect of food on the oral bioavailability of preladenant, a novel adenosine A(2A) receptor antagonist. This open-label, randomized, single-dose, 2-way crossover study evaluated the effects of a high-fat, high-calorie meal on the pharmacokinetics of preladenant and its metabolite (SCH434748) following oral...
The Parkinson Progression Marker Initiative (PPMI) is a comprehensive observational, international, multi-center study designed to identify PD progression biomarkers both to improve understanding of disease etiology and course and to provide crucial tools to enhance the likelihood of success of PD modifying therapeutic trials. The PPMI cohort will...
To determine the correspondence of in vivo quantitative estimates of brain uptake of fluorine 18-labeled flutemetamol with immunohistochemical estimates of amyloid levels in patients who underwent previous biopsy.
Cross-sectional study of ¹⁸F-flutemetamol positron emission tomography (PET) findings in patients with prior cortical biopsy specimen st...
The type 1 cannabinoid receptor (CB1) is a crucial modulator of synaptic transmission in brain and has been proposed as a potential therapeutic target in Parkinson's disease (PD), especially for treatment of levodopa-induced dyskinesias (LID). Our aim was to measure CB1 levels in brains of PD patients in vivo and to investigate the relation between...
Several studies have examined the link between the cannabinoid CB1 receptor and several neuropsychiatric illnesses, including schizophrenia. As such, there is a need for in vivo imaging tracers so that the relationship between CB1 and schizophrenia (SZ) can be further studied. In this paper, we present our first human studies in both healthy contro...
The type 1 cannabinoid receptor (CB1) is a crucial modulator of synaptic transmission in the brain. Animal and postmortem human data suggest that mutant huntingtin represses CB1 transcription. Our aim was to measure CB1 levels in the brains of Huntington disease (HD) patients in vivo.
Twenty symptomatic HD patients and 14 healthy controls underwent...
Pain and somatosensory processing involves an interaction of multiple neuronal networks. One result of these complex interactions is the presence of differential responses across brain regions that may be incompletely modeled by a straightforward application of standard general linear model (GLM) approaches based solely on the applied stimulus. We...
The promise of neuroimaging to speed up the discovery of drugs and the development in the neurosciences is high and there
is considerable enthusiasm for the wide-spread implementation of many techniques. However, there is a need to balance advocacy
with objectivity as we test the decision making value of differing imaging approaches and choose whic...
Brain neurochemistry can partially account for personality traits as a variance of normal human behavior, as has been demonstrated for monoamine neurotransmission. Positron emission tomography using fluorine 18-labeled MK-9470 now enables quantification of type 1 cannabinoid receptors (CB1R) in the brain.
To investigate whether there is a relations...
Objective measure of pain is valuable in drug discovery research and development of analgesics. Spinal cord is an important relay of the pain pathway, and fMRI offers an excellent opportunity to quantify pain using activation in the spinal cord induced by painful stimuli. fMRI literature of cervical spinal cord with regard to the spatial extent, in...
There is substantial evidence that the endocannabinoid system and in particular the type 1 cannabinoid receptor (CB1R) is involved in epilepsy. We evaluated the in vivo effect of chronic administration of the anti-epileptic drugs valproate (VPA) and levetiracetam (LEV) on rat brain CB1 receptors using the positron emission tomography (PET) tracer [...
The cannabinoid type-1 (CB1) receptor is one of the most abundant G-coupled protein receptors in the human body and is responsible for signal transduction of both endogenous and exogenous cannabinoids. The endocannabinoid system is strongly implicated in regulation of homeostasis and several neuropsychiatric disorders, obesity, and associated comor...
Most studies of pain, including chronic pain, agree that depression and pain are interrelated, although the neurobiology of this relationship remains unknown. Neuroimaging studies suggest a specific role of the prefrontal brain regions in the mechanisms of mood disorders and chronic pain. The present study examines the interrelationships between re...
Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study [Pain 2000;89:7-18]
The neurobiology of the interaction between pain and anxiety is unknown. The present study examined interrelationships between: regional brain chemistry (as identified by in vivo proton magnetic resonance spectroscopy [(1)H-MRS] in dorsolateral prefrontal cortex [DLPFC], orbitofrontal cortex [OFC], cingulate and thalamus), pain (as measured by shor...
In our previous in vivo proton magnetic resonance spectroscopy ((1)H MRS) study we found reduced levels of N-acetylaspartate in dorsolateral prefrontal cortex of chronic back pain patients. This study tests whether these chemical abnormalities can be detected in other pain states. Using (1)H MRS, we measured levels for N-acetylaspartate and other i...
The authors report the unusual case of a 58-year-old woman (MJP) suffering from left temporal throbbing headache, associated with confusion. Magnetic resonance imaging showed a 5 x 3 x 2 cm hematoma at the left posterior temporal--parietal junction (PTPJ). Repeated MRI of MJP's brain performed during a 4-month follow-up period showed decrease in he...
Anatomical, electrophysiological and functional neuroimaging studies show that the human brain is a complex network, where cortico-cortical and thalamo-cortical connections are organized in a specific pattern giving rise to brain function. In our recent studies we found that chemical connectivity between brain regions might be changed in different...
The neurobiology of cognitive interference is unknown. Previous brain imaging studies using the Stroop Color-Word (SCW) task indicate involvement of the cingulate cortex cognitive division. The present study examines interrelationships between regional brain N-Acetyl aspartate (NAA) levels (as identified by in vivo proton magnetic resonance spectro...
Human brain can be considered as a chemical network. The effects of cognitive interference (as measured by the Stroop Color-Word task) on connectivity pattern of N-acetyl aspartate (as identified by in vivo proton magnetic resonance spectroscopy), the marker of neuronal density and function, were examined across four right hemispheric regions using...
Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment
In our most recent study of normal aging, we found decreased concentration of multiple chemicals in the brain of middle-aged subjects, as compared with younger subjects using in vivo proton magnetic resonance spectroscopy ((1)H-MRS). We hypothesized that these age-dependent differences in brain chemistry changes might be a reflection of the multich...
We recently described the chemical network properties of the human brain using in vivo proton magnetic resonance spectroscopy ((1)H MRS). In a separate study of aging we found increased concentration of chemicals in the prefrontal and sensorimotor cortices up to the third decade of life, and subsequent decrease of chemical concentrations in the sam...
In our most recent study of normal aging, we found decreased concentration of multiple chemicals in the brain of middle-aged subjects, as compared with younger subjects using in vivo proton magnetic resonance spectroscopy (1H-MRS). We hypothesized that these age-dependent differences in brain chemistry changes might be a reflection of the multichem...
We recently described the chemical network properties of the human brain using in vivo proton magnetic resonance spectroscopy (1H MRS). In a separate study of aging we found increased concentration of chemicals in the prefrontal and sensorimotor cortices up to the third decade of life, and subsequent decrease of chemical concentrations in the same...
Age-related differences in the multichemical proton magnetic resonance spectroscopy (1H-MRS) profile of the human brain have been reported for several age groups, and most consistently for ages from neonates to 16-year-olds. Our recent 1H-MRS study demonstrated a significant age-related increase of total chemical concentration (relative to creatine...
We recently presented results in an in vivo study of human brain chemistry in 'physiologic' anxiety, i.e., the anxiety of normal everyday life. Normal subjects with high anxiety demonstrated increased concentration of chemicals in orbital frontal cortex (OFC) as compared to lower anxiety. In a separate study of aging we demonstrated a decrease of t...
The neurobiology of chronic pain, including chronic back pain, is unknown. Structural imaging studies of the spine cannot explain all cases of chronic back pain. Functional brain imaging studies indicate that the brain activation patterns are different between chronic pain patients and normal subjects, and the thalamus, and prefrontal and cingulate...
Magnetic resonance (MR) imaging techniques are rapidly expanding to provide anatomical, physiological, and biochemical information that can be used to noninvasively study the human brain across these dimensions. In this chapter we concentrate on the application of functional MR imaging and MR spectroscopy to understand the brain pathophysiology of...
The present study examines relationships between regional brain chemistry (as identified by localized in vivo three-dimensional single-voxel proton magnetic resonance spectroscopy (1H-MRS) and anxiety (as measured by the State-Trait Anxiety Inventory) in 16 healthy subjects. The relative concentrations of N-Acetyl aspartate, choline, glutamate, glu...
Brain chemistry was compared between 19 male and female normal volunteers in the age group 19-31 years, across six brain regions and nine metabolites using in vivo proton magnetic resonance spectroscopy. The relative concentrations of N-acetyl aspartate, choline, glutamate, glutamine, GABA, inositol, glucose, and lactate were measured relative to c...
Several groups have developed methods for registering an individual's 3D MRI by deforming a standard template. This achievement leads to many possibilities for segmentation and morphology that will impact nuclear medical research in areas such as activation and receptor studies. Accordingly, there is a need for methods that can assess the accuracy...
In the July 1996 issue of the ARCHIVES, Jenike et al1 presented results from a morphometric magnetic resonance imaging (MRI)–based brain segmentation study of obsessive-compulsive disorder (OCD). Compared with normal controls, patients with OCD had significantly less total white matter (extending previous findings of decreased posterior white matte...