Alzheimer's Disease: SPECT and PET Tracers for Beta-Amyloid Imaging

Valotassiou, Varvara; Archimandritis, Spyridon C.; Sifakis, N.; Papatriantafyllou, John; Georgoulias, Panagiotis

doi:10.2174/1567210204558602050

Cited by 3 publications

(3 citation statements)

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“…1−5 Therefore, the development of novel imaging agents specifically targeting Aβ plaques may lead to early diagnosis of AD and monitoring of the effectiveness of novel therapies for this devastating disease. 6−8 In past decades, a number of radiolabeled Aβ imaging agents based on highly conjugated Aβ specific dyes, such as Congo Red (CR) and thioflavin T (Th-T), have been developed and reported for single photon emission computed tomography (SPECT) and positron emission tomography (PET), 9,10 some of which have been tested in humans ( Figure 1). Among dozens of radioiodinated liagnds, [ 123 I]-6-iodo-2-(4′-dimethylamino)phenylimidazo [1,2]pyridine ([ 123 I]1, IMPY), a unique Th-T derivative with a [1,2,a]imidazopyridine ring, was the only SPECT tracer tested in humans.…”

Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Novel ¹⁸F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques

Cui

Wang

et al. 2012

J. Med. Chem.

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A series of fluoro-pegylated (FPEG) 2-pyridinylbenzoxazole and 2-pyridinylbenzothiazole derivatives were synthesized and evaluated as novel β-amyloid (Aβ) imaging probes for PET. They displayed binding affinities for Aβ(1-42) aggregates that varied from 2.7 to 101.6 nM. Seven ligands with high affinity were selected for (18)F labeling. In vitro autoradiography results confirmed the high affinity of these radiotracers. In vivo biodistribution experiments in normal mice indicated that the radiotracers with a short FPEG chain (n = 1) displayed high initial uptake into and rapid washout from the brain. One of the 2-pyridinylbenzoxazole derivatives, [(18)F]-5-(5-(2-fluoroethoxy)benzo[d]oxazol-2-yl)-N-methylpyridin-2-amine ([(18)F]32) (K(i) = 8.0 ± 3.2 nM) displayed a brain(2min)/brain(60min) ratio of 4.66, which is highly desirable for Aβ imaging agents. Target specific binding of [(18)F]32 to Aβ plaques was validated by ex vivo autoradiographic experiment with transgenic model mouse. Overall, [(18)F]32 is a promising Aβ imaging agent for PET and merits further evaluation in human subjects.

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Section: ■ Introductionmentioning

confidence: 99%

Synthesis and Evaluation of Novel ¹⁸F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques

Cui

Wang

et al. 2012

J. Med. Chem.

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“…Also, these radiotracers could provide treatment for AD patients early in the course of the disease when response to treatment is usually better. The development of plaque-binding compounds started with monoclonal antibodies against beta-amyloid (Aβ) and self-associating Aβ fragments, and was followed by analogues of histopathological dyes such as Congo Red, Chrysamine G, and Thioflavin T, which are used to stain SPs and NFTs in postmortem AD brain sections (Valotassiou et al, 2010;Villemagne et al, 2005). Recently, malononitrile analogues, which share the same binding site on Aβ peptides with the nonsteroidal anti-inflammatory drugs (NSAIDs), have been developed as potential tracers for Aβ imaging (Agdeppa et al, 2001(Agdeppa et al, , 2003aShoghi-Jadid et al, 2002).…”

Section: Beta Amyloid Imagingmentioning

confidence: 99%

The Clinical Use of SPECT and PET Molecular Imaging in Alzheimer’s Disease

Valotassiou¹,

Sifakis²,

Papatriantafyllou³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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Single photon emission computed tomography (SPECT) and positron emission tomography (PET) are functional nuclear medicine techniques which allow for accurate non-invasive in vivo measurements of a wide range of regional tissue functions in man. Brain functional imaging with SPECT and PET is based on the recording of the distribution of administered radionuclides in three dimensions, thus producing maps of brain biochemical and physiological processes. SPECT and PET techniques are able to image brain perfusion and metabolism, as well as various neurotransmission or other cellular processes using specific radioligands which mark in vivo receptors, transporters or enzymes. Brain SPECT and PET imaging-or molecular imaging-, has been applied to the study of Alzheimer's disease (AD) for over two decades. These functional neuroimaging approaches have the capability of identifying subtle pathophysiologic changes in the brain before structural changes are present (Xu et al., 2000). Therefore they possess greater potential for accurate and early diagnosis, monitoring disease progression, and better treatment followup. Furthermore, the application of SPECT and PET techniques to the study of AD has led to increased understanding of the underlying pathology and the disease processes and improved the differential diagnosis from other neurodegenerative causes of dementia. 2. Clinical applications of SPECT and PET molecular imaging in AD 2.1 Radiopharmaceuticals for SPECT and PET brain imaging Brain SPECT and PET imaging is performed using radiopharmaceuticals which utilize the highly selective properties of Blood Brain Barrier (BBB). The intact BBB has been a significant limitation whenever a nuclear imaging technique is employed to study the function of the living human brain since it may impede brain uptake of radiotracers (Jolliet Riant & Tillement, 1999). The main factors which regulate passage across the BBB are ionic selectivity and lipid solubility of substances (Costa, 2004). Osmotic pressure and specific and non-specific binding to plasma proteins, cell membranes and other components present in the bloodstream, may also affect the permeability of BBB and brain uptake of the administered radiopharmaceuticals (Tanaka & Mizojiri, 1999). In the absence of radiotracer www.intechopen.com The Clinical Spectrum of Alzheimer's Disease-The Charge Toward Comprehensive Diagnostic and Therapeutic Strategies 182 binding to these metabolic (biological) barriers, free diffusion of lipophilic small neutral compounds occurs directly through the endothelial cells of BBB (Waterhouse, 2003). 2.1.1 Properties and mechanisms of brain uptake Radiopharmaceuticals used for brain perfusion SPECT imaging are lipophilic and neutral compounds with limited protein binding, which penetrate freely the intact BBB by simple diffusion (Costa, 2004). They distribute in proportion to regional cerebral blood flow (rCBF) and remain trapped in neuronal tissue without redistribution for a suitable amount of time to permit SPECT imaging. Brain perfusion SPECT r...

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“…Along with the development of different tracers that can target beta-amyloid (9), tau protein (10), synaptic vesicle glycoprotein 2A (SV2A) density (11), acetylcholine (12), brain perfusion (13), and dopaminergic system (14), the role of radionuclide imaging, including PET and SPECT, in neurodegenerative diseases is well recognized. Usually, highly demanding production and transportation processes are needed for PET, especially if short-lived isotopes are used, whereas the half-life of SPECT isotopes is longer.…”

Section: Introductionmentioning

confidence: 99%

Multi-pinhole collimator design in different numbers of projections for brain SPECT

Huang,

Mok

2023

Front. Med.

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PurposeHigh resolution and sensitivity brain SPECT is promising for the accurate diagnosis of Alzheimer's disease (AD) and Parkinson's disease (PD). Multi-pinhole (MPH) collimators with a good performance in imaging small field-of-view (FOV) could be better used for brain SPECT. In this study, we aim to evaluate the impact of varying the number of pinholes and the number of projections on the performance of MPH brain SPECT.MethodsThe system design was based on a commercial clinical dual-head SPECT/CT scanner, with target spatial resolutions of 12 mm and 8 mm for AD and PD SPECT, respectively. In total, 1–25 pinholes were modeled for 64, 32, 16, 8, 4, and 2 projections. The 3D NURBS-based HUman Brain (NHUB) phantom was used in the analytical simulation to model 99mTc-HMPAO and 99mTc-TRODAT distributions. The 2D Derenzo hot-rod phantom and star phantom were used in Monte Carlo simulations to evaluate the spatial resolution and angular sampling performance of MPH. The influence of different detector positions was also evaluated for 2, 4, and 6 angular views. The projections were reconstructed using the 3D MPH ML-EM method. Normalized mean square error, coefficient of variation, and image profiles were evaluated.ResultsAlong with the decrease in the number of projections, more pinholes are required to achieve the optimum performance. For 32 projections, 9- and 7-pinhole collimators provide the best normalized mean square error (NMSE) to the coefficient of variation (COV) trade-off for 99mTc-HMPAO and 99mTc-TRODAT, respectively. Detector positions substantially affect the image quality for MPH SPECT for 2 and 4 angular views. The smallest rod size for the Derenzo hot-rod phantom, which could be resolved, is 7.9 mm for the MPH general purpose collimator (MPGP) with more than 16 projections and 6.4 mm for MPH high-resolution collimator (MPHR) with more than 8 projections.ConclusionThe number of pinholes affects the performance of the MPH collimator, especially when the projection views become fewer. More pinholes are required for fewer projections to provide better angular sampling in MPH for complex activity distributions. Detector positions affect the image quality of MPH SPECT for 2 and 4 angular views, where L-mode acquisition is slightly superior to H-mode. MPH collimators exhibited improved spatial resolution and angular sampling compared with both LEHR and single pinhole collimators.

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Alzheimer's Disease: SPECT and PET Tracers for Beta-Amyloid Imaging

Cited by 3 publications

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Synthesis and Evaluation of Novel ¹⁸F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques

Synthesis and Evaluation of Novel ¹⁸F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques

The Clinical Use of SPECT and PET Molecular Imaging in Alzheimer’s Disease

Multi-pinhole collimator design in different numbers of projections for brain SPECT

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Alzheimer's Disease: SPECT and PET Tracers for Beta-Amyloid Imaging

Cited by 3 publications

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Synthesis and Evaluation of Novel 18F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques

Synthesis and Evaluation of Novel 18F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques

The Clinical Use of SPECT and PET Molecular Imaging in Alzheimer’s Disease

Multi-pinhole collimator design in different numbers of projections for brain SPECT

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Product

Resources

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Synthesis and Evaluation of Novel ¹⁸F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques

Synthesis and Evaluation of Novel ¹⁸F Labeled 2-Pyridinylbenzoxazole and 2-Pyridinylbenzothiazole Derivatives as Ligands for Positron Emission Tomography (PET) Imaging of β-Amyloid Plaques