Synthesis of tritium‐labeled levetiracetam ((2S)‐2‐(2‐oxopyrrolidin‐1‐yl)butanamide) with high specific activity

Abstract

A method for the preparation of [³H]levetiracetam with a high specific activity of 98 Ci/mmol (3.6 TBq/mmol) is described. The radioligand proved to be highly useful for the labeling of specific levetiracetam binding sites in rat brain membrane preparations.

[11C]HCN Radiochemistry: Recent Progress and Future Perspectives

“…(LEV, (S)-α-ethyl-2-oxo-1-pyrrolidine acetamide) is a pyrrolidone drug widely used to treat epilepsy and other central nervous systems disorders. [49] The in vivo binding target of LEV was identified as synaptic vesicle protein 2 A (SV2 A). To elucidate how LEV interacts with the SV2 A to prevent epilepsy, its 11 C-labeled isotopologue, L-[ 11 C] levetiracetam ([ 11 C]LEV), was synthesized as a potential imaging probe for study the expression of SV2A in vivo.…”

Radiosynthesis of 11C-Levetiracetam: A Potential Marker for PET Imaging of SV2A Expression

“…18 Indeed, 11 C labeled S-aminobutanamide could be produced according to reported radio- synthesis of 11 C-labeled amino acids. 25 Therefore, we designed another radiosynthetic route of 11 C-LEV shown in Scheme 5.…”

“…Briefly, the bisulfite adduct 3 of propionaldehyde as preprecursor was in situ converted to the aminosulfonate 4 as the precursor (reaction with ammonia for 30 min just prior to the end of bombardment (EOB)). The sulfite group of the aminosulfonic salt 4 was replaced by 11 Ccyanide to yield 11 C-amnionitrile 5 in aqueous solution. The 11 C-amnionitrile 5 was followed by reaction with 4-chlorobutyryl chloride in basic conditions to generate compound 2 after removal of water and dried.…”

“…In mammals, this protein family is encoded by three different genes (SV2A, SV2B, and SV2C), of which SV2A is the most abundant and widely expressed product and is critical for proper nervous system function and has been demonstrated to be involved in vesicle trafficking . However, the completely molecular function of SV2A remains elusive, and it is still unknown how LEV interacts with the SV2A to prevent epilepsy …”

“…This indicates that LEV is the gold standard ligand for binding to SV2A and, as such, is preferable to all other compounds. Although the binding affinity of LEV to SV2A is moderate (pIC 50 = 6.1), the high selectivity of LEV for SV2A was previously clearly demonstrated using tritium labeling LEV and various preclinical and clinical studies. , Therefore, the development of labeled LEV for PET imaging is highly desirable and optimal for quantification of SV2A expression in vivo .…”