Synthesis and biological evaluation of iodine-125 iodocaramiphen. A potential M1 muscarinic imaging agent for SPECT

✍ Scribed by Daniel W. McPherson; F. F. (Russ) Knapp Jr.; Robert L. Hudkins

• Publisher: John Wiley and Sons
• Year: 1994
• Tongue: French
• Weight: 376 KB
• Volume: 34
• Category: Article
• ISSN: 0022-2135
• DOI: 10.1002/jlcr.2580340306

✦ Synopsis

Abstract

Iodocaramiphen (2) is a selective muscarinic antagonist which binds in vitro with high affinity and selectivity to the M~1~ subtype of the muscarinic receptor. We report the synthesis of iodine‐125 labeled iodocaramiphen ([^125^I]‐2) via a tributylstannyl intermediate (3) in 50% radiochemical yield with a specific activity greater than 1000 mCi/μmol. Biodistribution studies in female Fischer rats demonstrated that [^125^I]‐2 had significant cerebral localization (0.7% injected dose/gram) at 60 minutes post injection. The uptake of activity washed out rapidly from the brain, however, and did not demonstrate specific uptake in those cerebral regions rich in muscarinic receptors. In addition, preinjection with (±)‐QNB (5 mg/kg) blocked uptake of approximately 25% of the injected radiolabel in the brain at 2 hours. The non‐selectivity of 2 toward muscarinic receptors in vivo may result from the metabolism of 2 by various esterases or the affinity of 2 for sigma sites in the brain.