New Synthesis and Tritium Labeling of a Selective Ligand for Studying High-Affinity γ‑Hydroxybutyrate (GHB) Binding Sites

3-Hydroxycyclopent-1-enecarboxylic acid (HOCPCA, <b>1</b>) is a potent ligand for the high-affinity GHB binding sites in the CNS. An improved synthesis of <b>1</b> together with a very efficient synthesis of [<sup>3</sup>H]-<b>1</b> is described. The radiosynthesis employs in situ generated lithium trimethoxyborotritide. Screening of <b>1</b> against different CNS targets establishes a high selectivity, and we demonstrate in vivo brain penetration. In vitro characterization of [<sup>3</sup>H]-<b>1</b> binding shows high specificity to the high-affinity GHB binding sites.