Date of Graduation

5-2022

Document Type

Thesis

Degree Name

Bachelor of Science

Degree Level

Undergraduate

Department

Chemistry & Biochemistry

Advisor/Mentor

Adams, Paul D.

Committee Member/Reader

Coridan, Robert

Committee Member/Second Reader

Alrubaye, Adnan

Committee Member/Third Reader

Aloia, Lindsey

Abstract

The inhibition of histone deacetylase 6 (HDAC6) has been reported to alleviate the effects of neurodegenerative diseases such as Alzheimer’s disease. The brain-penetrant PET radioligand [18F]EKZ-001 has high affinity and selectivity towards HDAC6 and therefore suggests great promise in therapeutic treatment studies and development for neurodegenerative diseases. “Translation of HDAC6 PET imaging using [18F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs” has achieved an effective, fully automated method of producing [18F]EKZ-001 in compliance with current good manufacturing practices (cGMP) to support the translation of [18F]EKZ-001 PET for first-in-human studies. This cGMP compliantly produced radioligand was utilized in PET studies in non-human primates (NHPs), where it was determined that the HDAC6 inhibitor EKZ-317 achieves greater target occupancy than the HDAC6 inhibitor ACY-775. The developments made by this research have had significant impact on the progression of therapeutic treatment studies for neurodegenerative diseases. The success of a cGMP compliant method of [18F]EKZ-001 production has enabled the first-in-human [18F]EKZ-001 PET study, further paving the way to a potential treatment for neurodegenerative diseases. This editorial aims to overview “Translation of HDAC6 PET imaging using [18F]EKZ-001 – cGMP production and measurement of HDAC6 target occupancy in NHPs”, to analyze and highlight the impact and relevance of this research, and propose future considerations for research in this area.

Keywords

neurodegenerative diseases; therapeutic drug development; HDAC6; [18F]EKZ001; positron emission tomography

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