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Review
. 2023 Apr 4;28(7):3233.
doi: 10.3390/molecules28073233.

Radiolabeled Chalcone Derivatives as Potential Radiotracers for β-Amyloid Plaques Imaging

Pier Cesare Capponi  1 , Matteo Mari  2 , Erika Ferrari  2 , Mattia Asti  1
Affiliations
Review

Radiolabeled Chalcone Derivatives as Potential Radiotracers for β-Amyloid Plaques Imaging

Pier Cesare Capponi et al. Molecules. .

Abstract

Natural products often provide a pool of pharmacologically relevant precursors for the development of various drug-related molecules. In this review, the research performed on some radiolabeled chalcone derivatives characterized by the presence of the α-β unsaturated carbonyl functional group as potential radiotracers for the imaging of β-amyloids plaques will be summarized. Chalcones' structural modifications and chemical approaches which allow their radiolabeling with the most common SPECT (Single Photon Emission Computed Tomography) and PET (Positron Emission Tomography) radionuclides will be described, as well as the state of the art regarding their in vitro binding affinity and in vivo biodistribution and pharmacokinetics in preclinical studies. Moreover, an explanation of the rationale behind their potential utilization as probes for Alzheimer's disease in nuclear medicine applications will be provided.

Keywords: Alzheimer’s disease; chalcones; labeling; radionuclide; α,β-unsaturated carbonyl compounds.

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Conflict of interest statement

The authors declare no conflict of interest and the funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Chemical structure of [18F]-florbetapir (Amyvid) (A), [18F]-florbetaben (Neuraceq) (B), [18F]-flutemetamol (Vizamyl) (C), and [18F]-flortaucipir (Tauvid) (D).
Figure 2
Figure 2
Curcuminod (A), chalcone (B), dibenzylideneacetone (C), and dehydrozingerone (D) general structure. Substituents on the aromatic rings provide the specific derivative.
Figure 3
Figure 3
Synthetic pathway for the preparation of general [125I]-labeled chalcone derivatives (A) and structures of all the derivatives explored in [19] (B).
Figure 4
Figure 4
Brain uptakes at 2 and 30 min post injection of [125I]-labeled (A), [11C]-labeled (B), [18F]-labeled (C), [99mTc]- and [68Ga]-labeled (D) chalcone derivatives in normal mice and the relative ratios.
Figure 5
Figure 5
[11C]-labeling (A) and [18F]-labeling (B) reaction pathways for the preparation of radiotracers based on F- and FPEG-chalcones structure.
Figure 6
Figure 6
Reaction steps for the direct [18F]-fluorination of a chalcone aromatic ring starting from the iodinated precursor.
Figure 7
Figure 7
Structure of chalcone derivatives containing ethyleneoxy chains in para-position of 3-phenyl ring or an iodoallyloxy group in para-position of 1-phenyl ring.
Figure 8
Figure 8
Reaction steps for the labeling of [125I]18 and [125I]21.
Figure 9
Figure 9
General structure of an indole-chalcone (A). Indole-Chalcone derivatives studied by Cui et al. [31] (B).
Figure 10
Figure 10
Reaction steps for the labeling of [125I]iodophenyl-indole-chalcone ([125I]25).
Figure 11
Figure 11
Structures of some [99mTc]-labeled radiotracers able to target β-amyloid plaques obtained by a bifunctional approach as reported in [23,24,25,36].
Figure 12
Figure 12
Structures of [99mTc]-labeled BAT and MAMA-chalcone derivatives (compounds ([99mTc]32–35).
Figure 13
Figure 13
Structures of some [99mTc]-labeled radiotracers able to target β-amyloid plaques obtained by an integrated approach as reported in [22,39].
Figure 14
Figure 14
Synthetic steps for the preparation of [Cp99mTc(CO)3]-chalcone-mimic derivatives (compounds ([99mTc]36–38).
Figure 15
Figure 15
Synthesis of homodimer [68Ga]DTPA-chalcone derivative (compound [68Ga]39).
See this image and copyright information in PMC

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