Recent progress in the development of metal complexes as β-amyloid imaging probes in the brain

Abstract

In this review, we have focused on the recent progress in metal complexes that are able to bind to β-amyloid (Aβ) species. We have discussed various radioactive complexes of ^99mTc, ⁶⁸Ga, ⁶⁴Cu, ⁸⁹Zr, and ¹¹¹In, which were designed as Aβ imaging agents for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging, non-radioactive Re and Ru complexes as Aβ sensors using luminescence methods, and Gd³⁺ complexes as contrast agents for magnetic resonance imaging (MRI).

Fig. 1. Chemical structures of Aβ imaging probes designed for AD and CAA.

Fig. 2. Chemical structures of bifunctional chelators used for ^99mTc-labeled Aβ imaging probes.

Fig. 3. Chemical structures of ^99mTc/Re-labeled 2-arylbenzoxazoles and 2-arylbenzothiazoles conjugated with BAT and MAMA chelators.

Fig. 4. Chemical structures of ^99mTc–Ham complexes with bivalent amyloid ligands.

Fig. 5. Chemical structure of ^99mTc/Re-labeled styrylpyridyl conjugated with the N₃O chelator.

Fig. 6. Chemical structures of [M(CO)₃]⁺ (M = ^99mTc or Re) complexes with tridentate chelators.

Fig. 7. (A) In vitro autoradiography of [^99mTc]56 and [¹²⁵I]IMPY on contiguous brain sections of a patient with AD. Aβ deposits within the blood vessels were indicated by triangles and Aβ plaques in the cerebral parenchyma were indicated by arrows. (B) Fluorescence staining using thioflavin-S (ThS) on the same brain sections. Adapted from ref. 63.

Fig. 8. Chemical structures of 2-arylbenzothiazole derivatives conjugated with the [CpM(CO)₃] core.

Fig. 9. In vitro autoradiography of [^99mTc]68 binding in contiguous brain sections from a patient with AD (68 years old, female, frontal lobe) (A and C) and the same section stained with ThS (GFP filter) (B). Higher magnification images of A and the corresponding higher magnification images stained with ThS (D). Adapted from ref. 64.

Fig. 10. Chemical structures of Re(CO)₃–NHC complexes.

Fig. 11. Chemical structures of commonly designed chelators for ⁶⁸Ga³⁺.

Fig. 12. Chemical structures of ^nat/68Ga-labeled Aβ imaging agents.

Fig. 13. Chemical structures of ⁶⁴Cu-labeled 2-phenylbenzofuran derivatives conjugated with cyclen and DOTA.

Fig. 14. Chemical structures of ⁸⁹Zr- and ¹¹¹In-labeled mAbs and Aβ peptides.

Fig. 15. Immunostaining (A) and in vitro autoradiography (B) on brain sections of 8 month-old APPPS1-21 Tg mice (left) and age-matched WT mice (right). Red squares indicate cortical regions with known high Aβ deposition. Adapted from ref. 82.

Fig. 16. Chemical structures of non-radioactive ruthenium and rhenium complexes.

Fig. 17. Chemical structures of gadolinium complexes for MRI.