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

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 [C-carbonyl]BPTES ([C]BPTES) as a positron emission tomography (PET) probe for the first time and assessed its biodistribution in mice using PET. [C]BPTES was synthesized by the reaction of an amine precursor () with [C-carbonyl]phenylacetyl acid anhydride ([C]), which was prepared from [C]CO and benzyl magnesium chloride, followed by in situ treatment with isobutyl chloroformate. The decay-corrected isolated radiochemical yield of [C]BPTES was 9.5% (based on [C]CO) during a synthesis time of 40 min. A PET study with [C]BPTES showed high uptake levels of radioactivity in the liver, kidney, and small intestine of mice.