2-(4-Hydroxyphenyl)benzothiazole dicarboxylate ester TACN chelators for 64Cu PET imaging in Alzheimer's disease.

Abstract

Herein we report a new series of bifunctional chelators (BFCs) with high affinity for amyloid β aggregates, strong binding affinity towards Cu(II), and favorable lipophilicity for potential blood-brain barrier (BBB) penetration. The alkyl carboxylate ester pendant arms show high binding affinity towards Cu(II). The BFCs form stable 64Cu-radiolabeled complexes and exhibit favorable partition coefficient (log D) values of 0.75-0.95. Among the five compounds tested, 64Cu-YW-1 and 64Cu-YW-13 complexes exhibit significant staining of amyloid plaques in ex vivo autoradiography studies.

• Authors: Yujue Wang, Truc T Huynh, Nilantha Bandara, Hong-Jun Cho, Buck E Rogers, Liviu M Mirica
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Vol. 51 Issue 3 Pg. 1216-1224 (Jan 17 2022) ISSN: 1477-9234 [Electronic] England
• PMID: 34951428 (Publication Type: Journal Article)

Chemical References

• Amyloidogenic Proteins
• Benzothiazoles
• Chelating Agents
• Copper Radioisotopes
• Copper-64
• Radiopharmaceuticals

Topics

• Alzheimer Disease (drug therapy)
• Amyloidogenic Proteins (genetics, metabolism)
• Animals
• Benzothiazoles
• Chelating Agents (chemistry)
• Copper Radioisotopes
• Mice
• Mice, Transgenic
• Molecular Structure
• Mutation
• Positron-Emission Tomography
• Radiopharmaceuticals (chemical synthesis, pharmacology)