{"title":"Imaging Amyloid in the Human Brain: A Promising Tool for Improved Early Diagnosis and Treatment Monitoring in Alzheimer`s Disease","authors":"A. Drzezga, R. Perneczky","doi":"10.2174/1876388X01002010053","DOIUrl":"https://doi.org/10.2174/1876388X01002010053","url":null,"abstract":"Alzheimer's disease has turned into one of today's most important medical and social challenges. Currently, the clinical diagnosis of Alzheimer's disease can only be established after the onset of the first symptoms. However, widespread and irreversible neural damage has probably already occurred at this stage. Furthermore, currently available drugs for Alzheimer's disease only offer a symptomatic treatment that can delay the progression of symptoms, with no effect on the neurodegeneration itself. Many drugs currently being evaluated for disease modifying effects in Alzheimer's disease will probably show their greatest effect in very early, pre-dementia disease stages, before widespread neural damage has occurred. Therefore, novel positron emission tomography tracers for amyloid, one of the histopathological hallmarks of Alzheimer's disease, are currently under evaluation regarding their abilities for pre-dementia diagnosis and treatment monitoring. First studies suggest that these tracers are able to reliably detect amyloid pathology in vivo, and that amyloid imaging is a promising candidate for the purpose of an improved early diagnosis and follow-up of Alzheimer's disease. This article discusses recent findings in this area and their relevance for the early diagnosis and treatment monitoring in Alzheimer's disease.","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"2 1","pages":"53-57"},"PeriodicalIF":0.0,"publicationDate":"2010-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial: Functional Biomarkers for Alzheimer`s Disease","authors":"F. Nobili","doi":"10.2174/1876388X01002020010","DOIUrl":"https://doi.org/10.2174/1876388X01002020010","url":null,"abstract":"","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"2 1","pages":"10-11"},"PeriodicalIF":0.0,"publicationDate":"2010-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68127574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"(18F)FDG-PET as a Biomarker for Early Alzheimer's Disease","authors":"F. Nobili, S. Morbelli","doi":"10.2174/1876388X01002010046","DOIUrl":"https://doi.org/10.2174/1876388X01002010046","url":null,"abstract":"Fluorine)fluorodeoxiglucose-Positron Emission Tomgraphy ( 18 F FDG-PET) has gained a leading role in the diagnostic assessment of patients with cognitive complaints, notably Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). Together with morphological Magnetic Resonance Imaging (MRI) and cerebrospinal fluid biomarker assays it allows early identification of subjects with neurodegeneration of the AD-type, which is crucial in view of effective disease-modifying drugs. (18F)FDG-PET identifies hypometabolic regions in posterior cingulate-precuneus, posterior lateral and medial temporal-parietal association cortex, and in lateral frontal cortex. Hypometabolism in posterior cingulate-precuneus may be found even in MCI patients not yet converted to AD after a reasonable follow-up time and thus it might be a marker of memory deficit rather than of AD conversion. As (18F)FDG-PET is sensitive to synaptic dysfunction and depletion, hypometabolic areas can be detected before atrophy is highlighted by MRI in the same regions. The interpretation of the pathophysiological meaning of hypometabolism is discussed also in view of the most recent theory on the brain 'default mode network'. In longitudinal 1-year studies, (18F)FDG-PET has been shown an adequate tool to detect metabolic deterioration in AD patients better than amyloid-PET. It has been proposed as a surrogate biomarker to evaluate the effect of disease-modifying drugs in AD with a five times higher power than the commonly used neuropsychological scales. A flow-chart on the clinical use of (18F)FDG-PET is proposed, in which it is strongly recommended in MCI patients with suspected neurodegeneration.","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"2 1","pages":"46-52"},"PeriodicalIF":0.0,"publicationDate":"2010-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Is there Still a Place for Perfusion SPECT in the Diagnosis of Dementia","authors":"Klaus P. Ebmeier","doi":"10.2174/1876388X01002010040","DOIUrl":"https://doi.org/10.2174/1876388X01002010040","url":null,"abstract":"Although research interest within functional imaging has moved towards applications of MRI, such as BOLD and perfusion imaging, there is a wealth of clinical experience in emission tomographic imaging techniques that make the use of these modalities relevant for the decades to come. This review touches upon the technical and practical issues that distinguish SPECT from PET, describes perfusion and metabolic changes observed in the dementias, compares the clinical utility of the two techniques, and reports data on clinical sensitivity and specificity, as well as diagnostic head-to head comparisons in dementia, and specifically Alzheimer's disease. While few centres have a genuine choice between PET and SPECT, either appears to be good enough to help with the differential diagnosis of dementia in difficult cases.","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"2 1","pages":"40-45"},"PeriodicalIF":0.0,"publicationDate":"2010-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126526","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic and Blood Biomarkers of Alzheimer's Disease","authors":"P. Momeni, R. Ferrari","doi":"10.2174/1876388X01002010012","DOIUrl":"https://doi.org/10.2174/1876388X01002010012","url":null,"abstract":"Alzheimer's disease (AD) is the most prevalent form of dementia. AD is highly heritable, with a complex pattern. Although clinical diagnosis is based on accurate and well defined diagnostic criteria (NINCDS-ADRDA), the definite diagnosis relies on the postmortem pathological findings. The need for measures for the early detection of AD, as well as the need to distinguish between AD and other forms of dementia, has put great emphasis on the discovery of biomarkers for Alzheimer's disease. In clinical practice, there is need for non-invasive, accurate methods for the early detection and differential diagnosis of AD. The successful identification and development of the biomarkers, depends completely on the understanding of pathology, genetic and molecular mechanisms involved in the disease. As blood is a circulating dynamic tissue and transcription reflects the ongoing changes in the system, it makes the transcriptional profiling of the blood cells, potentially, the most sensitive source for transcriptional biomarkers. A systematic comparison of the genetic and proteomic blood biomarkers in patients and healthy controls can reveal additional potential candidates for AD. In the first part of this review, we would like to discuss the most recent genetic findings and their possible involvement in the pathogenesis of AD. In the second part, we review the blood biomarkers which can be derived from peripheral blood mononuclear cells (PBMC), serum, and plasma. We discus three main category of bio-molecules, namely DNA, RNA (miRNA and mRNA), and protein as well as their possible role in the hypothetical mechanisms involved in pathogenesis of AD. A dynamic interaction between the genetic findings through the whole genome association studies and biomarkers discovery can advance our knowledge of AD pathogenesis beyond the scope of each field independently. There are two major types of Alzheimer's disease 1) Early onset AD (EOAD) with the age of onset <65 and strong familial clustering, with an autosomal dominant mode of inheritance, comprising about 5% of all cases with diagnosis of Alzheimer's disease, 2) late onset Alzheimer's disease (LOAD), comprising 95% of AD cases with the age of onset beyond 65 and no significant familial aggregation. The rare EOAD, is mostly associated with the highly penetrant mutations in APP (Amyloid Precursor Protein) on","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"2 1","pages":"12-24"},"PeriodicalIF":0.0,"publicationDate":"2010-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Chincarini, M. Corosu, G. Gemme, P. Calvini, Roberta Monge, M. Penco, L. Rei, S. Squarcia, P. Boccacci, G. Rodriguez
{"title":"Automatic Morphological Analysis of Medial Temporal Lobe","authors":"A. Chincarini, M. Corosu, G. Gemme, P. Calvini, Roberta Monge, M. Penco, L. Rei, S. Squarcia, P. Boccacci, G. Rodriguez","doi":"10.2174/1876388X01002010031","DOIUrl":"https://doi.org/10.2174/1876388X01002010031","url":null,"abstract":"Research in Alzheimer's disease (AD) has seen a tremendous growth of candidate biomarkers in the last decade. The role of such established or putative biomarkers is to allow an accurate diagnosis of AD, to infer about its prognosis, to monitor disease progression and evaluate changes induced by disease-modifying drugs. An ideal biomarker should detect a specific pathophysiological feature of AD, not present in the healthy condition, in other primary dementias, or in confounding conditions. Besides being reliable, a biomarker should be detectable by means of procedures which must be relatively non-invasive, simple to perform, widely available and not too expensive. At present, no candidate meets these requirements representing the high standards aimed at by researchers. Among others, various morphological brain measures performed by means of magnetic resonance imaging (MRI), ranging from the total brain volume to some restricted regions such as the hippocampal volume, have been proposed. Nowadays the efforts are directed toward finding an automated, unsupervised method of evaluating atrophy in some specific brain region, such as the medial temporal lobe (MTL). In this work we provide an extensive review of the state of the art on the automatic and semi-automatic image processing techniques for the early assessment of patients at risk of developing AD. Our main focus is the relevance of the morphological analysis of MTL, and in particular of the hippocampal formation, in making the diagnosis of AD and in distinguishing it from other dementias.","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"2 1","pages":"31-39"},"PeriodicalIF":0.0,"publicationDate":"2010-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"How to Distinguish Dementia with Lewy Bodies from Alzheimer Disease","authors":"P. Tiraboschi, U. Guerra","doi":"10.2174/1876388X01002010058","DOIUrl":"https://doi.org/10.2174/1876388X01002010058","url":null,"abstract":"Dementia with Lewy (DLB) bodies is the most common type of degenerative dementia after Alzheimer Disease (AD). Although an accurate diagnosis of DLB is important for adequate prognosis and therapy, its differentiation from other dementias and, especially, from AD may be extremely challenging for clinicians, as highlighted by the high variability in reported sensitivity (0.22 - 0.83) and specificity (0.79 - 1.00) rates for a diagnosis of probable DLB applying current clinical criteria. Various kinds of imaging procedures, including conventional MRI and brain perfusion SPECT, have been proposed for improving diagnostic accuracy, especially for most controversial cases. Among such techiques, those using radioactive tracers measuring the striatal binding at pre-synaptic dopamine transporter sites or myocardial uptake in post-ganglionic sympathetic fibers have emerged as the most useful for diagnostic purposes.","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"2 1","pages":"58-62"},"PeriodicalIF":0.0,"publicationDate":"2010-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Chinnadurai, S. Berg, G. Nicolas, M. Walter, H. Rasch, J. Mueller‐Brand, S. Kneifel
{"title":"Monitoring and Predicting Response to Peptide Receptor Radionuclide Therapy: A Quantitative SPECT-CT Based Analysis~!2009-12-10~!2010-02-04~!2010-04-21~!","authors":"P. Chinnadurai, S. Berg, G. Nicolas, M. Walter, H. Rasch, J. Mueller‐Brand, S. Kneifel","doi":"10.2174/1876388X01002010001","DOIUrl":"https://doi.org/10.2174/1876388X01002010001","url":null,"abstract":"Purpose: A standard imaging protocol for monitoring and predicting the response to Peptide Receptor Radionuclide Therapy (PRRT) has not been established yet. The aim of this study was to evaluate the response to PRRT by quantitative SPECT-CT and assess the value of SPECT-CT over routine planar scintigraphy in predicting the outcome","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"2 1","pages":"1-9"},"PeriodicalIF":0.0,"publicationDate":"2010-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
P. Hazari, K. Chuttani, Nitin Kumar, R. Mathur, R. Sharma, Baljinder Singh, A. Mishra
{"title":"Synthesis and Biological Evaluation of Isonicotinic Acid Hydrazide Conjugated with Diethyelenetriaminepentaacetic Acid for Infection Imaging","authors":"P. Hazari, K. Chuttani, Nitin Kumar, R. Mathur, R. Sharma, Baljinder Singh, A. Mishra","doi":"10.2174/1876388X00901010033","DOIUrl":"https://doi.org/10.2174/1876388X00901010033","url":null,"abstract":"Introduction: Isonicotinic acid hydrazide (INH) was coupled to diethylenetriaminepentaacetic acid (DTPA) via amide linkage. Primary object of the present invention was to propose a novel INH derivative based on DTPA, which form stable complexes with most of lanthanides and transition metals in periodic table. Another object of the present invention was to introduce a chelating group in INH without compromising its biological activity for early diagnosis of infection using nuclear medicine and MR techniques. Methods: The DTPA-bis(INH) was synthesized in high yield using simple synthetic procedure. Radiochemical purity was ascertained chromatographically using different solvent system. Blood kinetics in rabbits and biodistribution in mice were studied. The ability of DTPA-bis(INH) to target infection site in vivo was assessed by gamma scintigraphic studies of normal rabbit and rabbit with induced tuberculosis. Preliminary clinical studies were done in patients with known tuberculoses lesions. Results: DTPA-bis(INH) was characterized using spectroscopic techniques. The complex was successfully labeled with 99m Tc radionuclide with more than 95% labeling efficiency. It was found stable up to 24h. Blood kinetics showed rapid first pass clearance with biological half life t1/2 (F) of 11 min. Biodistribution in tuberculose induced Balb/c mice showed target to muscle ratio 4.53 ± 0.89 after 4h post injection. Gamma scintigraphy of normal as well as rabbits with induced tuberculosis was carried out. An appreciable activity was visualized in liver and kidneys. In infection induced rabbit similar pattern was observed with the accumulation of activity at the tuberculose site at 4 h post injection. Clinical scintigraphy with 99m Tc-DTPA-bis(INH) clearly indicated the accumulation of the tracer at the tuberculose region in six patients (median age 46 years, range 28-69 years, females; n=2 and males; n=4) which were found positive for Mycobacterium tuberculosis in bacterial culture analysis. Conclusions: From the present work it can be concluded that the radiolabeled DTPA-bis(INH) accumulates at the site of infection.","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"1 1","pages":"33-42"},"PeriodicalIF":0.0,"publicationDate":"2009-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Nikolaus, R. Larisch,, M. Beu,, H. Vosberg,, F. Forutan, A. Wirrwar,, H. Müller
{"title":"Quantification of D2 Receptor Binding in the Rat Striatum Using SmallAnimal PET – The Impact of the Reference Tissue on the BindingPotential of [18F]N-Methyl-Benperidol","authors":"S. Nikolaus, R. Larisch,, M. Beu,, H. Vosberg,, F. Forutan, A. Wirrwar,, H. Müller","doi":"10.2174/1876388X00901010025","DOIUrl":"https://doi.org/10.2174/1876388X00901010025","url":null,"abstract":"In the present study, the binding potential (BP) of the D2 receptor radioligand ( 18 F)N-methyl-benperidol (( 18 F)FMB) was determined with in vivo saturation binding analysis using either cerebellum or parietal cortex as reference region. For the purpose of validation, BP additionally was determined in the same set of animals by computing the equilibrium ratios of the distribution volumes (V3''). With in vivo saturation binding analysis, the striatal BP as obtained with a cortical estimate for the free and non-specifically bound radioligand fell short of the BP as obtained with a cerebellar estimate by 70%. Similarly, with the equilibrium distribution volume method, the employment of a cortical REF led to a striatal V3'', which was 30% lower than the V3'' obtained with a cerebellar REF. The BP determined with in vivo saturation binding analysis and a cerebellar REF provided a closer approximation to the BP previously obtained with in vitro autoradiography relative to the BP determined with in vivo saturation binding analysis and a cortical REF. Findings show that in vivo saturation binding analysis is a feasible approach to obtain receptor binding parameters if scanner characteristics or other technical limitations preclude the kinetic modelling of binding data. However, caution should be exerted in choosing the reference tissue with regard to the intended investigation.","PeriodicalId":88754,"journal":{"name":"The open nuclear medicine journal","volume":"1 1","pages":"25-32"},"PeriodicalIF":0.0,"publicationDate":"2009-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"68126495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}