Neuroimaging Advances in Neurologic and Neurodegenerative Diseases

Risacher, Shannon L.; Saykin, Andrew J.

doi:10.1007/s13311-021-01105-7

Cited by 9 publications

(5 citation statements)

References 11 publications

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“…Thus, the use of small-molecule amyloid PET in clinical trials has contributed to the FDA approval of aducanumab, and the continued use of this biomarker in AD clinical trials has reinforced the use of PET imaging in drug development [ 38 ]. It is believed that amyloid PET imaging can offer tremendous and unconditional support in early diagnosis, patient selection, monitoring of the disease, and assessing the therapeutic effect of new drugs against AD [ 39 ]. However, monitoring the drug itself and its brain delivery over the BBB is still lacking, slowing the development of effective immunotherapies for neurological diseases.…”

Section: Discussionmentioning

confidence: 99%

Application of 89Zr-DFO*-immuno-PET to assess improved target engagement of a bispecific anti-amyloid-ß monoclonal antibody

Stergiou

Wuensche

Schreurs

et al. 2023

Eur J Nucl Med Mol Imaging

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Purpose The recent conditional FDA approval of Aducanumab (Adu) for treating Alzheimer’s disease (AD) and the continued discussions around that decision have increased interest in immunotherapy for AD and other brain diseases. Reliable techniques for brain imaging of antibodies may guide decision-making in the future but needs further development. In this study, we used 89Zr-immuno-PET to evaluate the targeting and distribution of a bispecific brain-shuttle IgG based on Adu with transferrin receptor protein-1 (TfR1) shuttling mechanism, mAbAdu-scFab8D3, designated Adu-8D3, as a candidate theranostic for AD. We also validated the 89Zr-immuno-PET platform as an enabling technology for developing new antibody-based theranostics for brain disorders. Methods Adu, Adu-8D3, and the non-binding control construct B12-8D3 were modified with DFO*-NCS and radiolabeled with 89Zr. APP/PS1 mice were injected with 89Zr-labeled mAbs and imaged on days 3 and 7 by positron emission tomography (PET). Ex vivo biodistribution was performed on day 7, and ex vivo autoradiography and immunofluorescence staining were done on brain tissue to validate the PET imaging results and target engagement with amyloid-β plaques. Additionally, [89Zr]Zr-DFO*-Adu-8D3 was evaluated in 3, 7, and 10-month-old APP/PS1 mice to test its potential in early stage disease. Results A 7-fold higher brain uptake was observed for [89Zr]Zr-DFO*-Adu-8D3 compared to [89Zr]Zr-DFO*-Adu and a 2.7-fold higher uptake compared to [89Zr]Zr-DFO*-B12-8D3 on day 7. Autoradiography and immunofluorescence of [89Zr]Zr-DFO*-Adu-8D3 showed co-localization with amyloid plaques, which was not the case with the Adu and B12-8D3 conjugates. [89Zr]Zr-DFO*-Adu-8D3 was able to detect low plaque load in 3-month-old APP/PS1 mice. Conclusion 89Zr-DFO*-immuno-PET revealed high and specific uptake of the bispecific Adu-8D3 in the brain and can be used for the early detection of Aβ plaque pathology. Here, we demonstrate that 89Zr-DFO*-immuno-PET can be used to visualize and quantify brain uptake of mAbs and contribute to the evaluation of biological therapeutics for brain diseases.

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Section: Discussionmentioning

confidence: 99%

Application of 89Zr-DFO*-immuno-PET to assess improved target engagement of a bispecific anti-amyloid-ß monoclonal antibody

Stergiou

Wuensche

Schreurs

et al. 2023

Eur J Nucl Med Mol Imaging

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“…Research has confirmed that neuroimaging technologies may precisely reflect the characteristics of brain function in neuropsychiatric disorders and therapeutic responses (Dan, 2019;Risacher and Saykin, 2021). To better understand the underlying mechanism of acupuncture, an increasing number of acupuncture research have started to explore the brain neural effects linked to therapeutic responses applied functional magnetic resonance imaging (fMRI) techniques (Cai et al, 2018;Zhang et al, 2021a).…”

Section: Introductionmentioning

confidence: 99%

Immediate neural effects of acupuncture manipulation time for stroke with motor dysfunction: a fMRI pilot study

Zhou,

Dai,

Feng

et al. 2024

Front. Neurosci.

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IntroductionAcupuncture is widely utilized as a beneficial intervention for the treatment of motor dysfunction after stroke, and its effectiveness depends on the stimulation dose. Manipulation time is an important factor affecting the dose. This trial aimed use fMRI to explore the immediate neural effects in stroke patients with motor dysfunction by different acupuncture manipulation times, to reveal the neural mechanism of acupuncture manipulation.MethodsThirty participants were divided into three groups according to different acupuncture times. Each group received the same acupoint prescription, although the continuous manipulation time of each acupoint in three groups was 1-min, 2-min, and 3-min, respectively. The NIHSS, FMA and fMRI-BOLD in each participant we obtained before and after acupuncture manipulation. Then, we used the regional homogeneity (ReHo) algorithm to analyze the changes of brain function and to compare the neural effects at different acupuncture manipulation times.ResultsThere were no significant differences in NIHSS and FMA scores between and within groups. Longitudinal analysis of ReHo values indicated that the right inferior frontal gyrus was activated in the 1-min group, the right insula in the 2-min group, and the right inferior temporal gyrus in the 3-min group. Compared with the 1-min group, the 2-min group showed the ReHo values of the right precentral gyrus was decreased, and the 3-min group showed the left cerebellum posterior lobe was increased, the right posterior cingulate gyrus and the right anterior cingulate gyrus were decreased. Compared with the 2-min group, the 3-min group showed the ReHo values of the right cerebellum anterior lobe was increased.ConclusionOur findings suggest that acupuncture at different manipulation times caused different changes of the neural effects in stroke patients, and the volume of activated voxel clusters is positively correlated with the manipulation time. Longer acupuncture manipulation could drive SMN and DMN in stroke patients, which may be the potential neurological mechanism of acupuncture manipulation affecting the recovery of motor dysfunction.

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“…It provides a major source for methods like MRI and PET scans used in the detection of early signs before the presentation of significant neurological changes. These imaging modalities have developed over time to be high resolution and could offer an early chance for detection, helping the physician regarding disease monitoring with respect to decision-making and tracking progression [ 4 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

Advancing the Frontier: Neuroimaging Techniques in the Early Detection and Management of Neurodegenerative Diseases

Akram,

Grezenko,

Singh

et al. 2024

Cureus

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Alzheimer's and Parkinson's diseases are among the most prevalent neurodegenerative conditions affecting aging populations globally, presenting significant challenges in early diagnosis and management. This narrative review explores the pivotal role of advanced neuroimaging techniques in detecting and managing these diseases at early stages, potentially slowing their progression through timely interventions. Recent advancements in MRI, such as ultra-high-field systems and functional MRI, have enhanced the sensitivity for detecting subtle structural and functional changes. Additionally, the development of novel amyloid-beta tracers and other emerging modalities like optical imaging and transcranial ultrasonography have improved the diagnostic accuracy and capability of existing methods. This review highlights the clinical applications of these technologies in Alzheimer's and Parkinson's diseases, where they have shown improved diagnostic performance, enabling earlier intervention and better prognostic outcomes. Moreover, the integration of artificial intelligence (AI) and longitudinal research is emerging as a promising enhancement to refine early detection strategies further. However, this review also addresses the technical, ethical, and accessibility challenges in the field, advocating for the more extensive use of advanced imaging technologies to overcome these barriers. Finally, we emphasize the need for a holistic approach that incorporates both neurological and psychiatric perspectives, which is crucial for optimizing patient care and outcomes in the management of neurodegenerative diseases.

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Neuroimaging Advances in Neurologic and Neurodegenerative Diseases

Cited by 9 publications

References 11 publications

Application of 89Zr-DFO*-immuno-PET to assess improved target engagement of a bispecific anti-amyloid-ß monoclonal antibody

Application of 89Zr-DFO*-immuno-PET to assess improved target engagement of a bispecific anti-amyloid-ß monoclonal antibody

Immediate neural effects of acupuncture manipulation time for stroke with motor dysfunction: a fMRI pilot study

Advancing the Frontier: Neuroimaging Techniques in the Early Detection and Management of Neurodegenerative Diseases

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