Radiofluorinated 3-(2{prime}-fluoroethyl)-2-thienylspiperone (FETS): Synthesis, pharmacologic characterization, tissue distribution and primate imaging of a selective radioligand for mapping D2 receptor sites by PET
- Emory Univ., Atlanta, GA (United States); and others
Abnormally high dopaminergic neurotransmission has been implicated in schizophrenia. A number of radiolabeled analogs of spiperone, a potent antipyschotic with a high (nanomolar) affinity for dopamine D2 receptors, have been synthesized for quantifying D2 receptors in humans. An undesired property accompanying high striatal uptake of radiolabeled spiperone (SPIP) analogs is high affinity for serotonin 5-IIT2 receptors. A potent spiperone analog which selectively binds to D2 receptors would be valuable in studying regional dopaminergic aberrations in schizophrenia. We have synthesized new potent radioligands [F-18] labeled 3-(2{prime}-fluoroethyl)-2-thienylspiperone (FETS) and 3-(3{prime}-fluoropropyl)-2-thienylspiperone (FPTS) for quantifying D2 receptors by PET. In vitro binding studies for D2 receptors in rat striatal homogenates using [H-3]raclopride afforded Ki`s (nM) of 1.07 for SPIP, 2.02 for FETS, 3.45 for FES and 5.45 for FPTS. In vitro binding studies for 5-HT2 receptors in rat cortical homogenates using [H-3]ketanserin afforded Ki`s (nM) of 1.86 for SPIP, 6.03 for FES, 20 for FPTS and 67 for FETS. Thus, FETS was found to be a potent and the most selective (Ki 5-HT2/Ki D2=33.5) spiperone ligand for D2 receptors. [F-18]FETS was synthesized in 41% E.O.B. by NCA K[F-18]/K222 exchange for tosylate from 3-(2{sup {prime}}-tosylethyl)-2-thienylspiperone in CH3CN at 100{degrees}C. HPLC purification afforded [F-18]FETS with a specific activity of 8 Ci/{mu}mole in a total synthesis time of 90 min. Following femoral vein injection in rats [F-18]FETS showed good uptake and retention in striatal (S) tissue (0.91% dose/g at 60 min) with clearance from the cerebellum (C) (0.24% dose/g at 60 min) giving S/C = 3.6 at 60 min. [F-18]FETS (6.0 mCi) was also administered to a rhesus monkey and showed high uptake and retention in the basal ganglia with S/C = 6.0 and 10.0 at 1 h and 2 h post injection respectively.
- OSTI ID:
- 441625
- Report Number(s):
- CONF-950603-; ISSN 0161-5505; TRN: 96:002093-0050
- Journal Information:
- Journal of Nuclear Medicine, Vol. 36, Issue Suppl.5; Conference: 42. annual meeting of the Society of Nuclear Medicine, Minneapolis, MN (United States), 12-15 Jun 1995; Other Information: PBD: May 1995
- Country of Publication:
- United States
- Language:
- English
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