Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease

Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease Publisher Pubmed

Jokar S¹ ; Behnammanesh H¹ ; Erfani M² ; Sharifzadeh M³ ; Gholami M³ ; Sabzevari O³ ; Amini M^{5, 6} ; Geramifar P⁷ ; Hajiramezanali M¹ ; Beiki D⁷

Show Affiliations

1. Department of Nuclear Pharmacy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
2. Radiation Application Research School, Nuclear Science and Technology Research Institute (NSTRI), Tehran, Iran
3. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran
4. Toxicology and Poisoning Research Centre, Tehran University of Medical Sciences, Tehran, Iran
5. Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
6. Drug Design and Development Research Center, Tehran University of Medical Sciences, Tehran, Iran
7. Research Center for Nuclear Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Bioorganic Chemistry Published:2020

Abstract

With respect to the main role of amyloid-β (Aβ) plaques as one of the pathological hallmarks in the brain of Alzheimer's patients, the development of new imaging probes for targeted detection of Aβ plaques has attracted considerable interests. In this study, a novel cyclopentadienyl tricarbonyl Technetium-99 m (99mTc) agent with peptide scaffold, 99mTc-Cp-GABA-D-(FPLIAIMA)-NH2, for binding to the Aβ plaques was designed and successfully synthesized using the Fmoc solid-phase peptide synthesis method. This radiopeptide revealed a good affinity for Aβ42 aggregations (Kd = 20 µM) in binding affinity study and this result was confirmed by binding to Aβ plaques in brain sections of human Alzheimer's disease (AD) and rat models using in vitro autoradiography, fluorescent staining, and planar scintigraphy. Biodistribution studies of radiopeptide in AD and normal rats demonstrated a moderate initial brain uptake about 0.38 and 0.35% (ID/g) 2 min post-injection, respectively. Whereas, AD rats showed a notable retention time in the brain (0.23% ID/g at 30 min) in comparison with fast clearance in normal rat brains. Normal rats following treatment with cyclosporine A as a p-glycoprotein inhibitor showed a significant increase in the radiopeptide brain accumulation compared to non-treated ones. There was a good correlation between data gathered from single-photon emission computed tomography/computed tomography (SPECT/CT) imaging and biodistribution studies. Therefore, these findings showed that this novel radiopeptide could be a potential SPECT imaging agent for early detection of Aβ plaques in the brain of patients with AD. © 2020 Elsevier Inc.

2. Recent Advances in the Design and Applications of Amyloid-Β Peptide Aggregation Inhibitors for Alzheimer’S Disease Therapy, Biophysical Reviews (2019)

3. Design of a New 99M99mtc-Radiolabeled Cyclo-Peptide As Promising Molecular Imaging Agent of Cxcr4 Receptor: Molecular Docking, Synthesis, Radiolabeling, and Biological Evaluation, Current Radiopharmaceuticals (2024)

4. Metal-Organic Frameworks: A Promising Option for the Diagnosis and Treatment of Alzheimer's Disease, Journal of Controlled Release (2023)

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Safura Jokar (3)

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Style	Citing Format
MLA	Jokar S, et al.. "Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease." Bioorganic Chemistry, vol. 99, no. , 2020, pp. -.
APA	Jokar S, Behnammanesh H, Erfani M, Sharifzadeh M, Gholami M, Sabzevari O, Amini M, Geramifar P, Hajiramezanali M, Beiki D (2020). Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease. Bioorganic Chemistry, 99(), -.
Chicago	Jokar S, Behnammanesh H, Erfani M, Sharifzadeh M, Gholami M, Sabzevari O, Amini M, Geramifar P, Hajiramezanali M, Beiki D. "Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease." Bioorganic Chemistry 99, no. (2020): -.
Harvard	Jokar S et al. (2020) 'Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease', Bioorganic Chemistry, 99(), pp. -.
Vancouver	Jokar S, Behnammanesh H, Erfani M, Sharifzadeh M, Gholami M, Sabzevari O, et al.. Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease. Bioorganic Chemistry. 2020;99():-.
BibTex	@article{ author = {Jokar S and Behnammanesh H and Erfani M and Sharifzadeh M and Gholami M and Sabzevari O and Amini M and Geramifar P and Hajiramezanali M and Beiki D}, title = {Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease}, journal = {Bioorganic Chemistry}, volume = {99}, number = {}, pages = {-}, year = {2020} }
RIS	TY - JOUR AU - Jokar S AU - Behnammanesh H AU - Erfani M AU - Sharifzadeh M AU - Gholami M AU - Sabzevari O AU - Amini M AU - Geramifar P AU - Hajiramezanali M AU - Beiki D TI - Synthesis, Biological Evaluation and Preclinical Study of a Novel 99Mtc-Peptide: A Targeting Probe of Amyloid-Β Plaques As a Possible Diagnostic Agent for Alzheimer's Disease JO - Bioorganic Chemistry VL - 99 IS - SP - EP - PY - 2020 ER -

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