Amyloid Imaging Agents Research Articles

Value of nuclide scintigraphy in the diagnosis and prognosis of cardiac amyloidosis.

Amyloidosis is a local or systemic disease caused by the deposition of misfolded proteins outside the cell, with rapid progression, and dire prognosis. Common types of cardiac amyloidosis are monoclonal immunoglobulin light chain amyloidosis (AL-CA) and transthyretin cardiac amyloidosis (ATTR-CA). Nuclear medicine examinations can be accurate, rapid, and non-invasive to help diagnose diseases and can effectively predict the prognosis of patients with CA. Technetium (99Tcm)-labeled bisphosphonate imaging has been included in the consensus of experts and has become the first-line imaging method for the diagnosis of ATTR-CA. 123I-metaiodoenzylguanidine (MIBG) as a norepinephrine analogue can effectively assess cardiac sympathetic innervation in patients with CA. Aβ- amyloid imaging agents such as 11C-pittsburgh compound B and 18F-flubetaben are expected to be new techniques for diagnosing AL-CA and incorporating them into cardiac staging systems for AL-CA patients in the future. New imaging agents such as 18F-NaF has been widely used in the diagnosis, treatment response monitoring, and prognosis assessment of CA. Summarizing the research value of nuclide imaging in CA may provide new ideas for clinical realization of early detection of CA and accurate assessment of disease prognosis.

Longitudinal evaluation of cardiac and extracardiac amyloid load in patients with AL and ATTR amyloidosis, measured by 124I-AT-01 PET/CT imaging

Abstract Background The amyloid imaging agent, 124I-AT-01 (124I-p5+14), is being developed for the diagnosis and monitoring of amyloidosis, of any type, by PET/CT imaging (1,2). PET/CT is an intrinsically quantitative imaging modality, and this reagent could provide a facile, first-line method for the diagnosis of amyloidosis as well as permit quantitative longitudinal imaging for monitoring progression or regression of disease, notably in the heart, of all amyloid patients. Here we describe an interim analysis of a case series of AL and ATTR patients who have been imaged at least twice with 124I-AT-01 with a minimum of 12 months between imaging (NCT designation pending). Radiotracer uptake has been quantified for the heart, liver, spleen and kidneys and changes in uptake reported. Purpose The goal was to quantitatively assess changes in organ-specific radiotracer uptake in AL and ATTR patients with previous cardiac uptake using manual region-of-interest methods. Methods The study will enroll patients with AL (n=10) and ATTR (n=10) who were previously imaged more than 12 months prior and who had positive uptake of 124I-AT-01 in the heart. To date, six patients have been imaged twice and one has had three evaluations since 2019. Patients received 37 or 74 MBq 124I-AT-01 and PET/CT imaging was performed at ∼5 h post injection. A fully manual 2D region of interest analysis was performed on three representative image views of the heart in the transaxial plane as well as the liver, spleen and kidneys. The blood pool was used as a reference tissue to determine standard uptake value ratios (SUVRmean). Changes in cardiac uptake of radiotracer were compared with contemporaneous NTproBNP measurements. Results The PET images were of high quality and readily interpretable and quantifiable (Figure 1A). In this early analysis of the data, both AL (n=2) and ATTR (n=4) have been evaluated. The mean time between first and second imaging was 30.3 ± 8.9 months. In the patients with ATTR amyloidosis, there was an average of a 7.9 ± 10% decrease in cardiac uptake of 124I-AT-01 after an average of 32.5 months from the first scan, in patients on silencers or stabilizers. In the AL patients, one had a 10% decrease and the other a 12% decrease in heart uptake. In some, these changes correlated with serum NTproBNP levels. A notable decrease in 124I-AT-01 binding in both AL patients was observed in the liver (45% and 59%) and spleen (75% and 73%) with one example shown in Figure 1B. No cases of increased radiotracer uptake were observed in the heart, consistent with these patients being stabilised with standard of care therapy. Conclusion Changes in cardiac amyloid load, based on differential uptake of radiotracer, can be seen by longitudinal imaging and quantified using 124I-AT-01 PET/CT imaging. This technique may play a valuable role not only in the early and accurate diagnosis of amyloidosis but also for monitoring changes in organ-specific amyloid load.

Toward the Noninvasive Diagnosis of Alzheimer's Disease: Molecular Basis for the Specificity of Curcumin for Fibrillar Amyloid-β.

Recent studies show that curcumin, a naturally fluorescent dye, can be used for the noninvasive optical imaging of retinal amyloid-β (Aβ) plaques. We investigated the molecular basis for curcumin’s specificity for hierarchical Aβ structures using molecular dynamics simulations, with a focus on how curcumin is able to detect and discriminate different amyloid morphologies. Curcumin inhibits and breaks up β-sheet formation in Aβ monomers. With disordered Aβ structures, curcumin forms a coarse-grained composite structure. With an ordered fibril, curcumin’s interaction is highly specific, and the curcumin molecules are deposited in the fibril groove. Curcumin tends to self-aggregate, which is finely balanced with its affinity for Aβ. This tendency concentrates curcumin molecules at Aβ deposition sites, potentially increasing the fluorescence signal. This is probably why curcumin is such an effective amyloid imaging agent.

Radiolabeled curcumin as β amyloid imaging and tumor targeting imaging agents

Curcumin, a polyphenolic compound, derived from the rhizomes of Curcuma longa L. Curcumin shows potential pharmacological action against numerous disorders, including cancer, neurodegenerative, and infection diseases. Curcumin-based molecular imaging agents could be useful for early detection of Alzheimer Disease and tumor and monitor the progress of therapy. Radiolabeled curcumin and its derivatives become promising compounds as imaging agents. In this review, radiolabeled curcumin bearing radionuclides including fluorine-18, Technetium-99m, Iodine-125, and Gallium-68 are reviewed as an effort to develop curcumin-based probes not only for β amyloid imaging but also for tumor imaging.

Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue

Amyloid-β (Aβ) fibrils exhibit self-propagating, molecular-level polymorphisms that may contribute to variations in clinical and pathological characteristics of Alzheimer's disease (AD). We report the molecular structure of a specific fibril polymorph, formed by 40-residue Aβ peptides (Aβ40), that is derived from cortical tissue of an AD patient by seeded fibril growth. The structure is determined from cryogenic electron microscopy (cryoEM) images, supplemented by mass-per-length (MPL) measurements and solid-state NMR (ssNMR) data. Previous ssNMR studies with multiple AD patients had identified this polymorph as the most prevalent brain-derived Aβ40 fibril polymorph from typical AD patients. The structure, which has 2.8-Å resolution according to standard criteria, differs qualitatively from all previously described Aβ fibril structures, both in its molecular conformations and its organization of cross-β subunits. Unique features include twofold screw symmetry about the fibril growth axis, despite an MPL value that indicates three Aβ40 molecules per 4.8-Å β-sheet spacing, a four-layered architecture, and fully extended conformations for molecules in the central two cross-β layers. The cryoEM density, ssNMR data, and MPL data are consistent with β-hairpin conformations for molecules in the outer cross-β layers. Knowledge of this brain-derived fibril structure may contribute to the development of structure-specific amyloid imaging agents and aggregation inhibitors with greater diagnostic and therapeutic utility.

Pre‐clinical dose ranging efficacy testing of ADx: A contrast agent for magnetic resonance imaging of amyloid burden in Alzheimer’s disease

AbstractBackgroundEarly detection of amyloid plaque deposits is crucial for identifying pre‐symptomatic Alzheimer’s disease (AD) patients. An amyloid imaging magnetic resonance imaging (MRI) contrast agent would have substantial utility in the clinic due to its ease of distribution and the standard use of MRI in AD patient workup. In this work, we describe dose‐ranging efficacy study of an amyloid‐targeted liposomal macrocyclic gadolinium (Gd) contrast agent, ADx‐001, for in vivo MRI of amyloid plaques.Method In vivo studies were performed in an APPswe/PSEN1dE9 double transgenic mouse model of early‐onset Alzheimer’s disease that develop amyloid plaques starting at 6‐7 months of age. ADx‐001 was tested at three dose levels: 0.10, 0.15 and 0.20 (mmol Gd/kg). At each dose level, ADx‐001 was tested in transgenic (n=6) and age‐matched wild‐type (mice that lacked both mutations) mice (n=6). MRI was performed on a 1 Tesla permanent magnet MR scanner using a T1‐weighted spin‐echo (T1w‐SE) sequence and a fast‐spin echo inversion recovery (FSE‐IR) sequence that approximates a fluid‐attenuated inversion recovery (FLAIR) sequence. Images were acquired pre‐contrast and at 4 days after intravenous administration of ADx‐001. Animals were euthanized after post‐contrast imaging for post‐mortem histological evaluation of amyloid plaques. Pre‐contrast and delayed post‐contrast MR images were qualitatively and quantitatively analyzed to determine sensitivity, specificity and accuracy against post‐mortem histological identification of Aβ plaque.ResultADx‐001‐enhanced MRI showed significant brain signal enhancement (p < 0.05) in transgenic mice (amyloid‐positive) relative to wild‐type (amyloid‐negative) mice in T1w‐SE (Figure 1) and FSE‐IR (Figure 2) images at all dose levels (Figure 3). ADx‐001‐enhanced T1w‐SE imaging showed high sensitivity (>80%) at 0.2 and 0.1 mmol Gd/kg dose levels while FSE‐IR showed high sensitivity (>80%) at 0.2 and 0.15 mmol Gd/kg doses (Table 1). ADx‐001‐enhanced MRI showed excellent specificity (100%) at all dose levels. Microscopy confirmed co‐localization of ADx‐001 with amyloid plaque deposits in cortex and hippocampus regions of the brain in transgenic mice (Figure 4).ConclusionADx‐001 demonstrated high sensitivity and excellent specificity for in vivo MRI of amyloid plaques in transgenic mice even at moderate and low concentrations. An MRI‐based amyloid imaging agent holds great promise for early detection of AD and potential therapeutic studies.

Recent Advances in the Synthesis and Applications of 2-Arylbenzothiazoles

This review firstly covers the applications of 2-arylbenzothiazoles as amyloid imaging agents, antitumor agents, and organic luminescent materials. Then we review the recent advances in the synthesis of 2-arylbenzothiazole derivatives. On the one hand, we introduce the approaches for construction of the 2-arylbenzothiazole core, including the following categories: (i) classic condensation of 2-aminothiophenols, (ii) direct arylation of benzothiazoles, (iii) intramolecular cyclization of thiobenzanilides, and (iv) tandem cyclization of anilines/ nitroarenes­ with elemental sulfur or sulfides. On the other hand, the transition-metal-catalyzed direct C–H functionalizations of 2-aryl­benzothiazoles are also involved in this review.1 Introduction2 Applications of 2-Arylbenzothiazoles3 Construction of the 2-Arylbenzothiazole Core4 Synthesis 2-Arylbenzothiazoles via Direct C–H Functionalization5 Conclusion

Consideration of the Residual Radioactivity of Amyloid Imaging Agent 18F-flutemetamol Adsorbed on Materials Used in Amyloid PET

In an amyloid PET for visualizing amyloid beta plaque accumulated in the brain, an amyloid imaging agent generally tends to adsorb to the inner walls of materials used in routes of administration to the patient. Therefore, we evaluated the adsorption of the amyloid imaging agent 18F-flutemetamol by measuring the residual radioactivity of the injection route material (intravenous catheter, extension tube, three-way stopcock) and the dispensed material (needle, syringe) in 35 patients during amyloid PET. The average actual radioactivity administered to the patients was 188.5±6.0 MBq (mean±standard deviation). When the radioactive concentration was 66.5±14.5 MBq/ml, the residual radioactivity was 1.4±0.2% for the injection route material, 0.8±0.3% for the dispensed material and 2.2±0.5% for both materials added based on the radioactivity of the amyloid imaging agent 18F-flutemetamol used for administration to the patient. There was a correlation between radioactive concentration and residual radioactivity. As the radioactive concentration increased, the residual radioactivity of all the materials tended to increase. Validation of adsorption to the tube and other materials used to administer patients can predict the residual radioactivity of the amyloid imaging agent 18F-flutemetamol prior to administration.

Fluorescent 1,4-Naphthoquinones To Visualize Diffuse and Dense-Core Amyloid Plaques in APP/PS1 Transgenic Mouse Brains.

Recent clinical approvals of brain imaging radiotracers targeting amyloid-β provided clinicians the tools to detect and confirm Alzheimer's disease pathology without autopsy or biopsy. While current imaging agents are effective in postsymptomatic Alzheimer's patients, there is much room for improvement in earlier diagnosis, hence prompting a need for new and improved amyloid imaging agents. Here we synthesized 41 novel 1,4-naphthoquinone derivatives and initially discovered 14 antiamyloidogenic compounds via in vitro amyloid-β aggregation assay; however, qualitative analyses of these compounds produced conflicting results and required further investigation. Follow-up docking and biophysical studies revealed that four of these compounds penetrate the blood-brain barrier, directly bind to amyloid-β aggregates, and enhance fluorescence properties upon interaction. These compounds specifically stain both diffuse and dense-core amyloid-β plaques in brain sections of APP/PS1 double transgenic Alzheimer's mouse models. Our findings suggest 1,4-naphthoquinones as a new scaffold for amyloid-β imaging agents for early stage Alzheimer's.

Long-term Changes in 18F-Flutemetamol Uptake in Nondemented Older Adults.

Longitudinal studies into the variability of F-Flutemetamol uptake are lacking. Therefore, the current study examined change in F-Flutemetamol uptake in 19 nondemented older adults (65 to 82 y old) who were either cognitively intact or had Mild Cognitive Impairment (MCI) who were scanned twice across 3.6 years. Baseline and follow-up composite SUVRs were significantly correlated (0.96, P<0.001). Significant increases in the composite SUVR from baseline to follow-up were observed (P=0.002). For the total sample, the average difference over this time period when using the composite SUVR was 6.8%. Similar results were seen in subsets of the total sample (MCI vs. cognitively intact, amyloid positive vs. negative). Finally, a Reliable Change Index that exceeded ±0.046 SUVR units would indicate a significant change of F-Flutemetamol. The current results extend the limited literature on longitudinal variability of F-Flutemetamol uptake across 3.6 years, which should give clinicians and researchers more confidence in the stability of this amyloid imaging agent in longer therapeutic and prevention trials in cognitive decline in MCI and Alzheimer disease.

Amyloid-Targeting PET Tracer [18F]Flutemetamol Accumulates in Atherosclerotic Plaques.

Atherosclerosis is characterized by the accumulation of oxidized lipids in the artery wall, which triggers an inflammatory response. Oxidized low-density lipoprotein (ox-LDL) presents amyloid-like structural properties, and different amyloid species have recently been recognized in atherosclerotic plaques. Therefore, we studied the uptake of the amyloid imaging agent [18F]Flutemetamol in atherosclerotic plaques. The binding of [18F]Flutemetamol to human carotid artery plaque was studied in vitro. In vivo uptake of the tracer was studied in hypercholesterolemic IGF-II/LDLR−/−ApoB100/100 mice and C57BL/6N controls. Tracer biodistribution was studied in vivo with PET/CT, and ex vivo by gamma counter and digital ex vivo autoradiography. The presence of amyloid, ox-LDL, and macrophages in the plaques was examined by immunohistochemistry. [18F]Flutemetamol showed specific accumulation in human carotid plaque, especially in areas positive for amyloid beta. The aortas of IGF-II/LDLR−/−ApoB100/100 mice showed large thioflavin-S-positive atherosclerotic plaques containing ox-LDL and macrophages. Autoradiography revealed 1.7-fold higher uptake in the plaques than in a lesion-free vessel wall, but no difference in aortic tissue uptake between mouse strains were observed in the in vivo PET/CT. In conclusion, [18F]Flutemetamol binds to amyloid-positive areas in human atherosclerotic plaques. Further studies are warranted to clarify the uptake mechanisms, and the potential of the tracer for in vivo imaging of atherosclerosis in patients.

Synthesis, Radioiodination and Biological distribution of 5-(5-(tributylstannyl) benzofuran-2-yl) pyridin-2-amine as an amyloid imaging agent

Synthesis, Radioiodination and Biological distribution of 5-(5-(tributylstannyl) benzofuran-2-yl) pyridin-2-amine as an amyloid imaging agent

2-(4'-Aminophenyl)benzothiazole Labeled with 99mTc-Cyclopentadienyl for Imaging β-Amyloid Plaques.

The development of a 99mTc-radiotracer for imaging of β-amyloid (Aβ) plaques with single photon emission computed tomography (SPECT) is strongly anticipated to provide a low cost and broadly accessible diagnostic tool for Alzheimer's disease (AD). Within this framework, 2-(4'-aminophenyl)benzothiazole, known to display affinity and specificity for Aβ plaques, has been joined to the tricarbonyl fac-[M(CO)3]+ (M = Re(I), 99mTc(I)) core through the cyclopentadienyl moiety to yield stable, neutral, and lipophilic complexes (Re-1 and 99mTc-1, respectively). The Re-1 complex was completely characterized with spectroscopic methods and was shown to selectively stain Aβ plaques on sections of human AD brain tissue. The 99mTc-1 complex displayed satisfactory initial brain uptake (0.53% ID/g at 2 min) and in vivo stability in healthy mice, while in transgenic 5xFAD mice, models for AD, a notable retention in the brain was noted (1.94% ID/g at 90 min). The results are encouraging and contribute to the effort of developing a SPECT amyloid imaging agent.

Synthesis and biological evaluation of curcumin analogs as β-amyloid imaging agents.

Detection of β-amyloid (Aβ) plaques in the brain is a very promising biomarker approach for early diagnosis of Alzheimer's disease (AD). A series of curcumin analogs (1,5-diphenyl-1,4-pentadien-3-one derivatives) were synthesized and evaluated. Specific binding to Aβ plaques was demonstrated in vitro using postmortem AD homogenates, and the fluorescent staining and autoradiography in vitro of postmortem AD brain sections were performed. Some compounds showed high binding affinities with Aβ plaques. Fluorescent staining indicated that compound 4e clearly stained Aβ plaques within AD brain sections. In biodistribution, radioiodinated ligand [125I]4e exhibited high brain uptake and favorable clearance from the brain. Autoradiography in vitro further confirmed the high affinities of [125I]4e. The results strongly suggested that [125I]4e might be developed into potential amyloid imaging agent for the detection of senile plaques in AD. [Formula: see text].

Specific Amyloid Binding of Polybasic Peptides In Vivo Is Retained by β-Sheet Conformers but Lost in the Disrupted Coil and All D-Amino Acid Variants.

The heparin-reactive, helical peptide p5 is an effective amyloid imaging agent in mice with systemic amyloidosis. Analogs of p5 with modified secondary structure characteristics exhibited altered binding to heparin, synthetic amyloid fibrils, and amyloid extracts in vitro. Herein, we further study the effects of peptide helicity and chirality on specific amyloid binding using a mouse model of systemic inflammation-associated (AA) amyloidosis. Peptides with disrupted helical structure [p5(coil) and p5(Pro3)], with an extended sheet conformation [p5(sheet)] or an all-D enantiomer [p5(D)], were chemically synthesized, radioiodinated, and their biodistribution studied in WT mice as well as transgenic animals with severe systemic AA amyloidosis. Peptide binding was assessed qualitatively by using small animal single-photon emission computed tomography/x-ray computed tomography imaging and microautoradiography and quantitatively using tissue counting. Peptides with reduced helical propensity, p5(coil) and p5(Pro3), exhibited significantly reduced binding to AA amyloid-laden organs. In contrast, peptide p5(D) was retained by non-amyloid-related ligands in the liver and kidneys of both WT and AA mice, but it also bound AA amyloid in the spleen. The p5(sheet) peptide specifically bound AA amyloid in vivo and was not retained by healthy tissues in WT animals. Modification of amyloid-targeting peptides using D-amino acids should be performed cautiously due to the introduction of unexpected secondary pharmacologic effects. Peptides that adopt a helical structure, to align charged amino acid side chains along one face, exhibit specific reactivity with amyloid; however, polybasic peptides with a propensity for β-sheet conformation are also amyloid-reactive and may yield a novel class of amyloid-targeting agents for imaging and therapy.

Validation of an electronic image reader training programme for interpretation of [18F]flutemetamol β-amyloid PET brain images.

ObjectivesAn electronic training programme (ETP) was developed for interpretation of images during routine clinical use of the PET amyloid imaging agent [18F]flutemetamol injection (VIZAMYL). This study was carried out to validate the ETP.Materials and methodsFive nuclear medicine technologists (NMTs) and five readers previously inexperienced in amyloid image interpretation were required to self-train using the ETP and pass a test to participate. A total of 305 [18F]flutemetamol PET images were then tested as the validation set, following preassessment and reorientation (where required) by one of five NMTs. Next, a new set of readers blinded to clinical information independently assessed all 305 images. Images had been acquired in previous studies from patients representing the full spectrum of cognitive capacity. When available, a standard of truth determined by histopathology or clinical history was used to derive sensitivity and specificity for image interpretation from this validation set. Randomly selected images (n=29) were read in duplicate to measure intrareader reproducibility. Images were read first without, and subsequently with anatomic images, if available.ResultsAll NMTs and all readers scored 100% on the qualifying test. The interpretation of 135 cases without anatomic image support resulted in sensitivity ranging from 84% to 94% (majority 94%, median 92%) and specificity ranging from 77% to 96% (majority 92%, median 81%). Inter-reader agreement was very high, with most κ scores more than 0.8. Intrareader reproducibility ranged from 93 to 100%.ConclusionThe self-guided ETP effectively trained new amyloid PET image readers to accurately and reproducibly interpret [18F]flutemetamol PET images.

Bis-pyridylethenyl benzene as novel backbone for amyloid-β binding compounds

Detection of cerebral β-amyloid (Aβ) by targeted contrast agents is of great interest for in vivo diagnosis of Alzheimer’s disease (AD). Partly because of their planar structure several bis-styrylbenzenes have been previously reported as potential Aβ imaging agents. However, these compounds are relatively hydrophobic, which likely limits their in vivo potential. Based on their structures, we hypothesized that less hydrophobic bis-pyridylethenylbenzenes may also label amyloid. We synthesized several bis-pyridylethenylbenzenes and tested whether these compounds indeed display improved solubility and lower LogP values, and studied their fluorescent properties and Aβ binding characteristics. Bis-pyridylethenylbenzenes showed a clear affinity for Aβ plaques on both human and murine AD brain sections. Competitive binding experiments suggested a different binding site than Chrysamine G, a well-known stain for amyloid. With a LogP value between 3 and 5, most bis-pyridylethenylbenzenes were able to enter the brain and label murine amyloid in vivo with the bis(4-pyridylethenyl)benzenes showing the most favorable characteristics. In conclusion, the presented results suggest that bis-pyridylethenylbenzene may serve as a novel backbone for amyloid imaging agents.

Non-Invasive Imaging of Amyloid Deposits in a Mouse Model of AGel Using 99mTc-Modified Nanobodies and SPECT/CT.

Gelsolin amyloidosis (AGel), also known as familial amyloidosis, Finnish type (FAF), is an autosomal, dominant, incurable disease caused by a point mutation (G654A/T) in the gelsolin (GSN) gene. The mutation results in loss of a Ca2+-binding site in the second gelsolin domain. Subsequent incorrect folding exposes a cryptic furin cleavage site, leading to the formation of a 68-kDa C-terminal cleavage product (C68) in the trans-Golgi network. This C68 fragment is cleaved by membrane type 1-matrix metalloproteinase (MT1-MMP) during secretion into the extracellular environment, releasing 8- and 5-kDa amyloidogenic peptides. These peptides aggregate and cause disease-associated symptoms. We set out to investigate whether AGel-specific nanobodies could be used to monitor amyloidogenic gelsolin buildup. Three nanobodies (FAF Nb1-3) raised against the 8-kDa fragment were screened as AGel amyloid imaging agents in WT and AGel mice using 99mTc-based single-photon emission computed tomography (SPECT)/X-ray tomography (CT), biodistribution analysis, and immunofluorescence (IF). The quantitative characteristics were analyzed in a follow-up study with a Nb11-expressing mouse model. All three nanobodies possess the characteristics desired for a99mTc-based SPECT/CT imaging agent, high specificity and a low background signal. FAF Nb1 was identified as the most potent, based on its superior signal-to-noise ratio and signal specificity. As a proof of concept, we implemented 99mTc-FAF Nb1 in a follow-up study of the Nb11-expressing AGel mouse model. Using biodistribution analysis and immunofluorescence, we demonstrated the validity of the data acquired via 99mTc-FAF Nb1 SPECT/CT. These findings demonstrate the potential of this nanobody as a non-invasive tool to image amyloidogenic gelsolin deposition and assess the therapeutic capacity of AGel therapeutics currently under development. We propose that this approach can be extended to other amyloid diseases, thereby contributing to the development of specific therapies.

Sondas moleculares para a deteção de placas β-amilóide na doença de Alzheimer

The formation of amyloid structures is a neuropathological feature that characterizes several neurodegenerative disorders, such as Alzheimer´s and Parkinson´s disease. Up to now, the definitive diagnosis of these diseases can only be accomplished by immunostaining of post mortem brain tissues with dyes such Thioflavin T and congo red. Aiming at early in vivo diagnosis of Alzheimer´s disease (AD), several amyloid-avid radioprobes have been developed for b-amyloid imaging by positron emission tomography (PET) and single-photon emission computed tomography (SPECT). The aim of this paper is to present a perspective of the available amyloid imaging agents, special those that have been selected for clinical trials and are at the different stages of the US Food and Drugs Administration (FDA) approval.

Technical Considerations in Brain Amyloid PET Imaging with 18F-Florbetapir.

Technical factors play a critical role in the production of best-quality amyloid PET images for interpretation. This article provides specific instructions and general technical information about PET brain scanning of β-amyloid neuritic plaques. The focus of tracer-specific information will be on (18)F-florbetapir (indications, contraindications, dosing, administration, uptake time, scanning time, acquisition, processing, biodistribution, radiation dose, adverse events, and display). General scanning information relevant to all amyloid-imaging agents will be also be presented (e.g., mechanism of uptake, safe handling, positioning, prevention of patient motion, processing, and artifacts).