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

Recent Advances in the Application Peptide and Peptoid in Diagnosis Biomarkers of Alzheimer’s Disease in Blood

“…And then, they modified it on the nanoporous zinc oxide with a high surface area to further improve the binding sensitivity and realize the detection of Aβ42 in CSF; the LOD can reach 12 ag/mL. Jokar et al (2020) replaced all L -amino acids with D-type amino acids on the basis of Pep1, capped the C-terminus with an amide bond, and added D -proline and D -phenylalanine to the N-terminus, thus reducing the sensitivity to proteases, increasing brain uptake and inhibiting the formation of Aβ aggregates ( Figure 3A ; Jokar et al, 2020 ). They successfully synthesized 99m Tc-Cp-GABA-D-(FPLIAIMA)-NH2 as a potential SPECT imaging agent for early detection of Aβ plaques in the brains of AD patients.…”

“… Peptides from phage display library screening methods. (A) Transform the peptide obtained from phage display screening to get SPECT imaging agent ( Jokar et al, 2020 ); (B) schematic overview of the strategy for bacterial library screening used FACS ( Matis et al, 2017 ). Reproduced with permission.…”

Metals in Imaging of Alzheimer’s Disease

“…Jokar et al designed a 99m Tc agent 148 with a lipophilic peptide scaffold, 99m Tc-Cp-GABA-D-(FPLIAIMA)-NH 2 [97] (Figure 35). The affinity of complexes 145-147 for Aβ plaques was evaluated with confocal microscopy on human AD brain sections.…”

“…Jokar et al designed a 99m Tc agent 148 with a lipophilic peptide scaffold, 99m Tc-Cp-GABA-D-(FPLIAIMA)-NH2 [97] (Figure 35). Binding affinity studies were carried out on Aβ aggregation, and the respective observed values of K d and B max were 20.22 ± 7.26 µM and 201,700 ± 8750.89 bound molecules/plaque.…”

Amyloid ß-Targeted Inhibitory Peptides for Alzheimer’s Disease: Current State and Future Perspectives

“…To overcome these problems, modified peptides have been generated (18) with D-amino acids, retro-inverso cyclization, fluorination, as well as N-methylation of the ester bond (19). With this knowledge, peptides could be potential candidates for inhibiting Aβ conformational transitions, self-assembly, and toxicity against neurons, and promotion of the pathways of the nontoxic fibrillation and early diagnosis of Alzheimer' s disease (20). This chapter provides an overview of the therapeutic potential peptides as Aβ aggregation inhibitors.…”