A two-step one-pot radiosynthesis of the potent dopamine D2/D3 agonist PET radioligand [11C]MNPA

✍ Scribed by C. Steiger; S. J. Finnema; L. Raus; M. Schou; R. Nakao; K. Suzuki; V. W. Pike; H. V. Wikström; C. Halldin

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: French
• Weight: 295 KB
• Volume: 52
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.1583

✦ Synopsis

Abstract

(R)‐(−)‐2‐[^11^C]Methoxy‐N‐n‐propylnorapomorphine ([^11^C]MNPA ([^11^C]2)) is an agonist radioligand of interest for imaging D~2~/D~3~ receptors in vivo. Here we sought to develop an improved radiosynthesis of this radioligand. Reference 2 was synthesized in nine steps with an overall yield of about 5%, starting from codeine. Trimethylsilyldiazomethane proved to be a practical improvement in comparison to diazomethane in the penultimate methylation step. A protected precursor for radiolabeling ((R)‐(−)‐2‐hydroxy‐10,11‐acetonide‐N‐n‐propylnoraporphine, 4) was prepared from (R)‐(−)‐2‐hydroxy‐N‐n‐propylnorapomorphine (1) in 30% yield. [^11^C]2 was prepared from 4 via a two‐step one‐pot radiosynthesis. The first step, methylation of 4 with [^11^C]methyl triflate, occurred in quantitative radiochemical yield. The second step, deprotection of the catechol moiety with HCl and heat, yielded 60–90% of [^11^C]2 giving an overall incorporation yield from [^11^C]methyl triflate of 60–90%. In a typical run more than 1 GBq of [^11^C]2, was produced from carbon‐11 generated from a 10‐min proton irradiation (16 MeV; 35 µA) of nitrogen–hydrogen target gas. The radiochemical purity of [^11^C]2 was > 99% and specific radioactivity at the time of injection was 901±342 GBq/µmol (n=10). The total synthesis time was 35–38 min from the end of radionuclide production. The identity of [^11^C]2 was confirmed by comparing its LC‐MS/MS spectrum with those of reference 2 and (R)‐(−)‐10‐methoxy‐2,11‐dihydroxy‐N‐n‐propylnoraporphine. Copyright © 2009 John Wiley & Sons, Ltd.