The Glutaminase-1 Inhibitor [¹¹C-carbony]BPTES: Synthesis and Positron Emission Tomography Study in Mice

• Main Authors: Yiding Zhang (Author), Katsushi Kumata (Author), Lin Xie (Author), Yusuke Kurihara (Author), Masanao Ogawa (Author), Tomomi Kokufuta (Author), Nobuki Nengaki (Author), Ming-Rong Zhang (Author)
• Format: Book
• Published: MDPI AG, 2023-07-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Bis-2-(5-phenylacetamido-1,3,4-thiadiazol-2-yl)ethyl sulfide (BPTES) is a selective inhibitor of glutaminase-1 (GLS1), consequently inhibiting glutaminolysis. BPTES is known for its potent antitumor activity and plays a significant role in senescent cell removal. In this study, we synthesized [¹¹C-carbonyl]BPTES ([¹¹C]BPTES) as a positron emission tomography (PET) probe for the first time and assessed its biodistribution in mice using PET. [¹¹C]BPTES was synthesized by the reaction of an amine precursor () with [¹¹C-carbonyl]phenylacetyl acid anhydride ([¹¹C]<b>2</b>), which was prepared from [¹¹C]CO₂ and benzyl magnesium chloride, followed by in situ treatment with isobutyl chloroformate. The decay-corrected isolated radiochemical yield of [¹¹C]BPTES was 9.5% (based on [¹¹C]CO₂) during a synthesis time of 40 min. A PET study with [¹¹C]BPTES showed high uptake levels of radioactivity in the liver, kidney, and small intestine of mice.

Item Description

10.3390/ph16070963
1424-8247