Application of a novel phenylpiperazine formation reaction to the radiosynthesis of a model fluorine-18-labeled radiopharmaceutical (18FTFMPP).
The labeled serotonin agonist 3-[18F]fluoro-N-(alpha,alpha,alpha-trifluoro-m-tolyl)piperazine (18FTFMPP) was prepared rapidly using the labeling procedure for trifluorotoluenes, [18F]fluoro-for-nitro exchange, followed by an alumina-supported bis-alkylation. After normal-phase HPLC purification, the labeled product was obtained in 20-32% (n = 20) decay-corrected radiochemical yield with a radiochemical purity > 98% and a specific activity of 100 GBq/mumol. The synthesis time including purification was 3 h. The receptor binding affinity of FTFMPP to rat brain membranes was found to be similar to that of the nonfluorinated parent compound (TFMPP). Although TFMPP has been proposed by others as an agent for the imaging of serotonin receptors, only minimal receptor-mediated uptake was observed.
Mishani
E
E
Mallinckrodt Institute of Radiology, Washington University, Saint Louis, MO 63110, USA.
Cristel
M E
ME
Dence
C S
CS
McCarthy
T J
TJ
Welch
M J
MJ
D000818:Animals; D001921:Brain / Q000378:metabolism; D005462:Fluorine Radioisotopes; D066298:In Vitro Techniques; D007553:Isotope Labeling; D008024:Ligands; D008566:Membranes / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D011985:Receptors, Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
C107999:3-fluoro-N-(alpha,alpha,alpha-trifluoro-3-tolyl)piperazine; D005462:Fluorine Radioisotopes; D008024:Ligands; D010879:Piperazines; D019275:Radiopharmaceuticals; D011985:Receptors, Serotonin; D018490:Serotonin Agents