A new perspective for advanced positron emission tomography–based molecular imaging in neurodegenerative proteinopathies

Perani, Daniela; Iaccarino, Leonardo; Lammertsma, Adriaan A.; Windhorst, Albert D.; Edison, Paul; Boellaard, Ronald; Hansson, Oskar; Nordberg, Agneta; Bottlaender, Michel; Brooks, David J.; Carroll, Michael A.; Chalon, Sylvie; Gee, Anthony; Gerhard, Alexander; Halldin, Christer; Herholz, Karl; Herth, Matthias M.; Hinz, Rainer; Knudsen, Gitte M.; Kühnast, Bertrand; López-Picón, Francisco R.; Moresco, Rosa María; Pappatà, Sabina; Rinne, Juha O.; Rodriguez‐Vieitez, Elena; Santiago-Ribeiro, Marie Joao; Turkheimer, Federico; Laere, Koen Van; Varrone, Andrea; Vercouillie, Johnny; Winkeler, Alexandra

doi:10.1016/j.jalz.2019.02.004

Cited by 20 publications

(23 citation statements)

References 265 publications

(381 reference statements)

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“…Non-invasive detection of central pathologies is indispensable for understanding the mechanism underlying AD continuum and for facilitating early and differential diagnosis ( 28 , 222 – 225 ). TSPO-PET is still the most powerful imaging tool for AD-associated neuroinflammation but is currently facing two challenges.…”

Section: Discussionmentioning

confidence: 99%

PET Imaging of Neuroinflammation in Alzheimer’s Disease

Zhou

Kong

et al. 2021

Front. Immunol.

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Neuroinflammation play an important role in Alzheimer’s disease pathogenesis. Advances in molecular imaging using positron emission tomography have provided insights into the time course of neuroinflammation and its relation with Alzheimer’s disease central pathologies in patients and in animal disease models. Recent single-cell sequencing and transcriptomics indicate dynamic disease-associated microglia and astrocyte profiles in Alzheimer’s disease. Mitochondrial 18-kDa translocator protein is the most widely investigated target for neuroinflammation imaging. New generation of translocator protein tracers with improved performance have been developed and evaluated along with tau and amyloid imaging for assessing the disease progression in Alzheimer’s disease continuum. Given that translocator protein is not exclusively expressed in glia, alternative targets are under rapid development, such as monoamine oxidase B, matrix metalloproteinases, colony-stimulating factor 1 receptor, imidazoline-2 binding sites, cyclooxygenase, cannabinoid-2 receptor, purinergic P2X7 receptor, P2Y12 receptor, the fractalkine receptor, triggering receptor expressed on myeloid cells 2, and receptor for advanced glycation end products. Promising targets should demonstrate a higher specificity for cellular locations with exclusive expression in microglia or astrocyte and activation status (pro- or anti-inflammatory) with highly specific ligand to enable in vivo brain imaging. In this review, we summarised recent advances in the development of neuroinflammation imaging tracers and provided an outlook for promising targets in the future.

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Section: Discussionmentioning

confidence: 99%

PET Imaging of Neuroinflammation in Alzheimer’s Disease

Zhou

Kong

et al. 2021

Front. Immunol.

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“…Concomitantly to biomarker research, positron emission tomography (PET) techniques have paved the way for breakthroughs to assess pathophysiology in vivo in FTD 66 . In particular, PET imaging of tau burden represents one of the most recent and promising applications in neurodegenerative dementias 67 , and to date a number of tau tracers have been developed, such as [ 18 F]flortaucipir (formerly known as [ 18 F]AV1451), [ 18 F]T807, and [ 11 C]PBB3 68, 69 .…”

Section: Looking For Neuropathology and Prognostic Markersmentioning

confidence: 99%

“…New-generation tracers are currently under evaluation to overcome the non-specific/off-target binding, as binding has been reported in non-tau diseases such as in C9orf72 mutation or svPPA, which are mainly associated with TDP-43 pathology 80– 83 . Furthermore, the development of PET tracers able to specifically bind 3R or 4R tauopathies would have remarkable applications in clinical practice 66 .…”

Section: Looking For Neuropathology and Prognostic Markersmentioning

confidence: 99%

Recent advances in understanding frontotemporal degeneration

Borroni

Benussi

2019

F1000Res

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Frontotemporal degeneration (FTD) is a heterogeneous spectrum of neurodegenerative disorders characterized by diverse clinical presentations, neuropathological characteristics, and underlying genetic causes. In the last few years, several advances in the knowledge of clinical and biological aspects have been accomplished and three major scenarios have emerged that will represent the core issues in the FTD scene over the next few years. Foremost, the development of cerebrospinal fluid and blood biomarkers as well as neuroimaging techniques will aid the pursuit of new diagnostic and prognostic markers able to identify the ongoing proteinopathy and predict disease progression, which is key in identifying and stratifying patients for enrolment in clinical trials as well as evaluating response to treatment. On the other hand, current research has focused on the first attempts to slow down or revert disease progression, with the identification of disease modulators associated with disease onset and the ongoing development of the first pharmacological treatments for both sporadic and genetic FTD. Future research will certainly improve our knowledge of FTD and possibly open up a new era of disease-modifying therapies for this still-orphan disorder.

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“…Innate pathology triggers inflammation that induces an increase in the expression of mitochondrial 18-kDa translocator protein (TSPO) in the microglia. TSPO is the main target for the PET tracers currently used for imaging neuroinflammation in vivo [1][2][3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Direct Comparison of [18F]F-DPA with [18F]DPA-714 and [11C]PBR28 for Neuroinflammation Imaging in the same Alzheimer’s Disease Model Mice and Healthy Controls

et al. 2021

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Purpose In this study we compared the recently developed TSPO tracer [18F]F-DPA, with [18F]DPA-714 and [11C]PBR28 by performing in vivo PET imaging on the same Alzheimer’s disease mouse model APP/PS1-21 (TG) and wild-type (WT) mice with all three radiotracers. Procedures To compare the radiotracer uptake, percentage of injected dose/mL (%ID/mL), standardized uptake value ratios to cerebellum (SUVRCB), and voxel-wise analyses were performed. Results The peak uptake of [18F]F-DPA was higher than 4.3% ID/mL, while [18F]DPA-714 reached just over 3% ID/mL, and [11C]PBR28 was over 4% ID/mL in only one brain region in the WT mice. The peak/60-min uptake ratios of [18F]F-DPA were significantly higher (p < 0.001) than those of [18F]DPA-714 and [11C]PBR28. The differences in [18F]F-DPA SUVRCB between WT and TG mice were highly significant (p < 0.001) in the three studied time periods after injection. [18F]DPA-714 uptake was significantly higher in TG mice starting in the 20–40-min timeframe and increased thereafter, whereas [11C]PBR28 uptake became significant at 10–20 min (p < 0.05). The voxel-wise analysis confirmed the differences between the radiotracers. Conclusions [18F]F-DPA displays higher brain uptake, higher TG-to-WT SUVRCB ratios, and faster clearance than [18F]DPA-714 and [11C]PBR28, and could prove useful for detecting low levels of inflammation and allow for shorter dynamic PET scans.

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A new perspective for advanced positron emission tomography–based molecular imaging in neurodegenerative proteinopathies

Abstract: A new perspective for advanced positron emission tomography-based molecular imaging in neurodegenerative proteinopathies.

Cited by 20 publications

References 265 publications

PET Imaging of Neuroinflammation in Alzheimer’s Disease

PET Imaging of Neuroinflammation in Alzheimer’s Disease

Recent advances in understanding frontotemporal degeneration

Direct Comparison of [18F]F-DPA with [18F]DPA-714 and [11C]PBR28 for Neuroinflammation Imaging in the same Alzheimer’s Disease Model Mice and Healthy Controls

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